Macrophages in Systemic Lupus Erythematosus: A Bibliometric Analysis of Research Trends and Emerging Frontiers

Summary

This study systematically delineates the research landscape and evolving frontiers of the field of systemic lupus erythematosus and macrophages from 2016 to 2025 using bibliometric analysis.

Abstract

This study systematically analyzed 1,197 articles on the role of macrophages in systemic lupus erythematosus (SLE) published from 2016 to 2025 using bibliometric methods based on the Web of Science Core Collection. The analysis examined publication trends, collaborative networks, research themes, and the knowledge base to elucidate the current research landscape, core research forces, and frontier evolution in this field. The number of publications peaked at 154 in 2022, while annual citations increased overall from 184 in 2016 to 9,030 in 2025, indicating active and impactful research. China ranked first in publication volume (379 articles), whereas the United States led in total citations (18,838) and international collaboration centrality. Shanghai Jiao Tong University and Karolinska Institutet were the most productive institutions, with 23 articles each. Frontiers in Immunology (impact factor = 5.9; Journal Citation Reports quartile 1) was the most productive journal. Keyword timeline clustering identified 13 major research themes, including key components of innate immunity such as neutrophil extracellular traps, dendritic cells, and Toll-like receptors, as well as adaptive immunity involving T cells, B cells, and plasmacytoid dendritic cells. These themes also included core mechanisms such as macrophage polarization, the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, and apoptotic cell clearance, along with clinical hotspots such as lupus nephritis, macrophage activation syndrome, and rheumatoid arthritis. The evolution of research hotspots reflects a progression from early basic mechanisms of apoptotic cell and immune complex clearance to refined regulation of cytokines, innate immunity, and adaptive immunity, and finally to studies of signaling pathway-targeted therapy, clinical management, and multicenter validation, with “pathway” and “multicenter diagnosis” standing out as current research frontiers.

Introduction

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies, immune complex deposition, and multi-organ inflammation^1,2. Despite substantial advances in diagnostic approaches and therapeutic strategies over recent decades, SLE continues to cause severe damage to the kidneys, hematological system, and central nervous system^3,4,5. Existing treatments, including glucocorticoids, immunosuppressants, and biologic agents, generally have limited therapeutic efficacy and are associated with adverse effects to varying degrees^6,7,8. Cell engineering strategies, such as chimeric antigen receptor T (CAR-T) cell therapy, have shown the potential to achieve durable drug-free remission in SLE through deep depletion of autoreactive B cells^9,10,11. As key members of the innate immune system, macrophages perform crucial functions in immune complex clearance, efferocytosis of apoptotic cells, and cytokine secretion, thereby maintaining immune homeostasis^11,12. Accumulating evidence indicates that multiple forms of macrophage dysfunction are implicated in SLE pathogenesis^13,14,15. Dysregulated macrophage polarization into proinflammatory M1 versus anti-inflammatory M2 phenotypes has been consistently observed in lupus nephritis, where M1 macrophages promote tissue damage while M2 macrophages contribute to tissue repair as well as fibrotic remodeling^16,17. Excessive formation of neutrophil extracellular traps (NETs) and aberrant activation of interferon signaling pathways further amplify macrophage-mediated inflammatory responses^18,19,20. Consequently, macrophage dysfunction has emerged not only as a central node in SLE pathogenesis but also as a promising therapeutic target²¹.

The past decade has witnessed a rapid expansion of publications focusing on the role of macrophages in SLE, spanning diverse research directions, including efferocytosis, NETosis, macrophage polarization, metabolic reprogramming, and targeted modulation of signaling pathways^{22,23,24,25,26}. However, the burgeoning literature also brings challenges, including fragmented research themes, unclear identification of core research forces, and ambiguous mapping of frontier evolution, underscoring the urgent need for a systematic overview of the current research landscape. Bibliometrics employs mathematical and statistical methods to quantitatively analyze the distributional characteristics and evolutionary patterns of knowledge carriers, providing objective data on publication trends, collaborative networks, research hotspots, and frontier dynamics^{27,28,29,30,31}. While bibliometric approaches have been successfully applied to knowledge mapping in SLE immunotherapy, biomarker discovery, and related fields, bibliometric mapping focused specifically on macrophages in SLE remains limited^32,33,34. This study retrieves relevant literature from the Web of Science Core Collection database spanning 2016 to 2025 and employs CiteSpace, VOSviewer, and Scimago Graphica to conduct multidimensional visual analyses. By examining publication outputs, country/region and institutional collaborations, author and journal networks, keyword co-occurrence and timeline clustering, as well as citation burst detection, this study aims to systematically elucidate the current research status, core research forces, thematic evolution, and emerging frontiers in the field of macrophages in SLE, thereby providing an objective knowledge map and directional reference for future investigations.

Protocol

No ethical approval or informed consent was required for this study, as all data were derived from publicly available bibliographic records in the Web of Science Core Collection database. No human participants, animals, or clinical samples were involved in this research.

Data acquisition and search strategy

Data were retrieved from the Web of Science Core Collection (WOSCC) database on a single date (April 27, 2026) to ensure data consistency and reproducibility. The search query employed Boolean operators with the following structure: TS=("Lupus Erythematosus, Systemic" OR "Systemic Lupus Erythematosus" OR "Lupus Erythematosus Disseminatus") AND TS=("macrophage*"). Document types were restricted to articles and review articles. The publication period ranged from January 1, 2016, to December 31, 2025. A total of 1,197 valid papers were retained for subsequent bibliometric analysis.

Analytical tools

An analytical pipeline incorporating multiple software packages was used. CiteSpace (Research Resource Identifier [RRID]: SCR_020932) was used for keyword timeline clustering and citation burst analysis³⁵. VOSviewer (RRID: SCR_016598) was used to construct and visualize coauthorship networks for countries/regions, institutions, and authors, and to generate keyword co-occurrence maps³⁶. Scimago Graphica was used to generate country/region collaboration network visualizations from network files exported from VOSviewer³⁷. Basic statistical calculations and figure preparation were performed using WPS Excel and GraphPad Prism (RRID: SCR_002798). The overall bibliometric workflow is illustrated in Figure 1.

Parameter configuration in CiteSpace and VOSviewer

In CiteSpace, the time slice was set from 2016 to 2025 with 1-year intervals. The g-index (k = 10) was selected as the node selection threshold. The Pathfinder pruning algorithm was applied twice: first to simplify each individual time slice network, and again after merging all slices to reduce visual complexity. In VOSviewer, the LinLog/modularity algorithm was chosen for network layout optimization. Node sizes were weighted by document counts or citation frequencies, depending on the specific analysis. For country/region collaboration mapping using Scimago Graphica, node diameters reflected publication volumes, and link thickness represented collaboration intensities between countries.

Results

Annual publication output

Between 2016 and 2025, a total of 1,197 articles on macrophages in SLE were published. The annual publication volume fluctuated, starting at 112 in 2016, peaking at 154 in 2022, and then decreasing slightly to 133 in 2025. Over the same period, annual citation counts increased overall from 184 to 9,030, with minor fluctuations, indicating a progressive rise in academic impact in this field (Figure 2).

Country/region contributions and transnational collaboration networks

A total of 76 countries/regions contributed to research on macrophages in SLE. The top 10 countries/regions ranked by publication volume are presented (Table 1). China ranked first with 379 articles (31.7% of total), followed by the United States (311 articles, 26.0%), Japan (74 articles), England (59 articles), and Germany (57 articles). In terms of total citations, the United States led with 18,838 citations, far exceeding China’s 8,935 citations. Notably, England, Sweden, and Germany exhibited the highest mean citations per paper (66, 64, and 57, respectively), reflecting their high-impact contributions despite moderate publication volumes. The total link strength was highest for the United States (178), followed by England (78) and Germany (78), with China close behind at 77, indicating a level of international collaboration intensity comparable to that of the major European countries. These findings suggest that while the United States occupies a central position in the global collaboration network, both European nations and China also demonstrate strong collaborative activity.

Three major groups were identified in the country/region collaboration network. One group included Germany, Greece, Iran, Italy, Japan, the Netherlands, and Switzerland; another comprised Canada, France, Poland, Spain, Sweden, and the United Kingdom; and the third consisted of China, Mexico, the United States, and Australia (Figure 3A). The chord diagram further reveals the intensity of bilateral collaborations among the most productive countries/regions, highlighting the dominant roles of the United States and China in coauthorship linkages (Figure 3B). The annual publication trends of the top 10 countries/regions from 2016 to 2025 show that China’s output increased steadily, rising from 18 articles in 2016 to 70 articles in 2025. The United States demonstrated a relatively stable but slightly declining trend, starting at 51 articles in 2016 and ending at 21 articles in 2025. Japan, England, Germany, and other European countries maintained modest yet consistent contributions throughout the decade. Overall, the temporal patterns reveal a shift in research leadership: while the United States dominated the early years, China emerged as the most prolific contributor in the latter half of the observation period (Figure 3C).

Research institutions and collaboration networks

A total of 417 institutions contributed to this field. The top 10 institutions by publication volume are presented (Table 2). The institutional collaboration network revealed five major clusters (Figure 4A). Cluster 1 (red) comprised 12 institutions, including Harvard Medical School, Brigham & Women’s Hospital, Yale University, University of Washington, University of Michigan, and Shanghai Jiao Tong University. Cluster 2 (green) consisted of nine institutions, predominantly from China, such as Peking University, Central South University, Sun Yat-sen University, and the University of Hong Kong. Cluster 3 (blue) included eight institutions, mainly from eastern China, such as Huazhong University of Science and Technology, Nanjing University, Soochow University, and Southern Medical University. Cluster 4 (yellow) comprised seven institutions, including Fudan University, Anhui Medical University, University of Cambridge, Monash University, University of Melbourne, University of Toronto, and Chulalongkorn University. Cluster 5 (purple) also contained seven institutions, including the Chinese Academy of Sciences, the University of Chinese Academy of Sciences, the Karolinska Institutet, the Karolinska University Hospital, the Zhejiang Chinese Medical University, the Zhejiang University, and the University of Houston.

Shanghai Jiao Tong University and Karolinska Institutet shared the highest output with 23 articles each, followed by Sun Yat-sen University (21 articles), Huazhong University of Science and Technology (20 articles), and Nanjing University (20 articles). Among the top 10, seven were from China, while the remaining three were Karolinska Institutet (Sweden), the University of Washington (United States), and Harvard Medical School (United States) (Figure 4B). In terms of citations, the University of Washington received 2,095 citations, ranking first, followed by Karolinska Institutet (1,929), Harvard Medical School (1,265), and Central South University (926). Notably, NIAMSD (National Institute of Arthritis and Musculoskeletal and Skin Diseases) had only 13 articles but accumulated 2,124 citations, reflecting exceptionally high impact per paper. The distribution of the top 10 productive institutions by country/region is shown. China dominated the list with eight institutions, whereas Sweden and the United States each contributed one institution. In contrast, the top 10 institutions by citation count exhibited a different pattern: the United States contributed five institutions, China contributed three institutions, namely Central South University, Chinese Academy of Sciences, and Sun Yat-sen University, Sweden contributed Karolinska Institutet, and Canada contributed the University of Toronto (Figure 4C). This disparity indicates that although Chinese institutions lead in research quantity, American and European institutions tend to have higher per-paper impact and broader recognition.

Journal publication and citation analysis

A total of 417 journals published articles on macrophages in SLE from 2016 to 2025. The top 10 journals by publication volume are listed (Table 3). Frontiers in Immunology ranked first with 108 articles, followed by Lupus (38 articles), International Journal of Molecular Sciences (31 articles), Journal of Immunology (26 articles), and Arthritis & Rheumatology (24 articles). In terms of total citations, Frontiers in Immunology also led with 6,104 citations, substantially exceeding other journals. Nature Reviews Rheumatology had only 11 articles but accumulated 1,364 citations, reflecting high per-paper impact. Among the top 10 journals, seven were in Journal Citation Reports (JCR) Q1, two in Q2, and one in Q3. The journal co-citation network revealed five major clusters (Figure 5A). Cluster 1 included high-impact immunology journals such as Nature Reviews Rheumatology, Annals of the Rheumatic Diseases, Journal of Autoimmunity, and Autoimmunity Reviews. Cluster 2 comprised Frontiers in Immunology, Clinical Immunology, International Immunopharmacology, and International Journal of Molecular Sciences. Cluster 3 contained Journal of Immunology, Proceedings of the National Academy of Sciences, Nature Communications, and Immunity. Cluster 4 included Arthritis & Rheumatology, Lupus, Pediatric Rheumatology, Rheumatology International, Biomedicines, and Clinical and Experimental Rheumatology. Cluster 5 consisted of Autoimmunity, Clinical Rheumatology, Frontiers in Medicine, and International Journal of Life Sciences.

The bubble chart illustrates the relationship between publication volume, citation count, and journal impact factor among the top 10 productive journals (Figure 5B). Frontiers in Immunology exhibited the largest bubble (highest publications and citations), followed by International Journal of Molecular Sciences and Arthritis & Rheumatology. Journals with high impact factors, such as Arthritis & Rheumatology (impact factor [IF] = 10.9, Q1) and Autoimmunity Reviews (IF = 8.3, Q1), showed moderate publication volumes but strong citation performance. The bar chart of co-cited journals highlights the most influential sources in terms of citation frequency (Figure 5C). In terms of co-citation frequency, the top five journals were ranked as follows: Journal of Immunology, Frontiers in Immunology, Lupus, Annals of the Rheumatic Diseases, and Arthritis & Rheumatology. Other frequently co-cited journals included Nature, Nature Immunology, Proceedings of the National Academy of Sciences, and Immunity. This distribution underscores the foundational role of classic immunology journals and the growing influence of open-access and specialty journals in this research domain.

Author collaboration networks and academic impact analysis

A total of 787 authors contributed to the macrophages in the SLE field. The author collaboration network was divided into five major clusters (Figure 6A). Cluster 1 included Sun, L.Y., and a group of Chinese researchers focusing on macrophage polarization and lupus nephritis. Cluster 2 featured Kaplan, M.J., Elkon, K.B., Barnes, B.J., and Carmona-Rivera, C., representing a highly interconnected group working on NETs and efferocytosis. This cluster aligns with current research frontiers, as NETosis and impaired clearance of apoptotic cells are recognized as key drivers of SLE pathogenesis. Cluster 3 comprised Cao, X.T., Lu, Q.J., Zhao, M., and others, focusing on epigenetic regulation and autoimmunity. Cluster 4 included Mohan, C., Davidson, A., and Putterman, C., who have contributed extensively to lupus nephritis and biomarker discovery. Cluster 5 contained Dong, C., Ji, J., and others, primarily investigating macrophage-related signaling pathways.

The top 10 authors by publication volume are presented (Figure 6B). Kaplan, M.J. ranked first with 12 articles, followed by Mohan, C. (10 articles), Deng, G.M. (10 articles), Lu, Q.J. (9 articles), and Sun, L.Y. (8 articles). Notably, Kaplan, M.J., also led in citation count with 1,957 citations, far exceeding other authors. Elkon, K.B. (1,834 citations) and Carmona‑Rivera, C. (1,410 citations) also demonstrated exceptionally high per-paper impact. In terms of country/region distribution among top-cited authors, the United States contributed seven of the top 10, and Germany (Munoz, L.E.), China (Lu, Q.J.), and Iran (Sahebkar, A.) contributed one each (Figure 6C). This pattern indicates that although Chinese authors appear frequently in the productivity ranking, US-based researchers currently dominate in terms of academic influence.

Overall, the author collaboration network reveals distinct research communities: one centered on NETs and efferocytosis (Cluster 2) and another focused on macrophage polarization and lupus nephritis (Cluster 1), reflecting the two major hot topics in this field. The high citation counts of Kaplan, Elkon, and Carmona-Rivera underscore the growing recognition of innate immune mechanisms, particularly NET-mediated inflammation and defective clearance of dying cells, as critical areas for future therapeutic intervention.

Keyword clustering and evolution of research hotspots

The keyword co-occurrence network included 196 nodes and 254 links, with a network density of 0.0133 (Figure 7A). Table 4 lists the top 10 keywords ranked by occurrence count and centrality. The most frequent keyword was “systemic lupus erythematosus” (666 occurrences), followed by “expression” (186), “activation” (157), “rheumatoid arthritis” (149), and “macrophages” (144). In terms of centrality, which reflects a keyword’s bridging role in the research network, “autoimmune” (0.31), “autoimmune diseases” (0.30), and “macrophage” (0.30) exhibited the highest values, indicating their pivotal positions in connecting diverse research topics across the field. Macrophage activation syndrome was also among the most frequent keywords.

The keyword timeline clustering analysis covered 2016–2025. Early-stage research (2016–2019) was dominated by foundational clusters, including #6 erythematosus, #9 autoimmune diseases, and #12 autoimmune disease, focusing on basic clinical and immunological characteristics of SLE, with core keywords such as systemic lupus erythematosus, macrophages, and inflammation. During 2020–2023, research priorities shifted toward mechanistic clusters, with #1 NETs, #3 lupus nephritis, and #4 T cells gaining prominence. Keywords such as polarization, regulation, and NETs emerged as central themes, reflecting growing attention to interactions and regulatory mechanisms between innate and adaptive immune cells. In the most recent period (2023–2025), the emerging clusters #0 macrophage activation syndrome, #2 gene expression, and #11 apoptotic cells became dominant, indicating a shift toward in-depth molecular mechanisms, targeted inhibition strategies, and translational therapeutic applications.

Keyword burst analysis (Figure 7B) identified the top 25 terms with the strongest citation bursts, highlighting rapidly growing research priorities. Early burst keywords, such as apoptotic cells and tumor necrosis factor alpha, reflected foundational studies on inflammation and cell death. More recent bursts included apoptosis, risk, management, and pathway, indicating a shift toward translational research, therapeutic targets, and clinical applications. Notably, terms like therapy and pathway have maintained strong bursts into 2025, signaling their status as current research frontiers.

Together, the statistical results and the various mapping analyses systematically elaborate the research focus, thematic structure, and developmental trends of macrophage-related research in SLE (Figure 7C and Table 4). These findings reveal a clear trajectory from descriptive studies of immune cell function to in-depth investigations of innate immune pathways, with an increasing emphasis on translating basic research into novel therapeutic strategies for SLE and its complications.

Bibliometric analysis of references

From the co-citation network, the most frequently cited references were foundational and high-impact contributions in SLE immunopathology, macrophage biology, and related therapeutic research. Anders HJ (2020, Nat Rev Dis Primers) ranked first with 35 citations³⁸, followed by Jing C (2020, Proc Natl Acad Sci USA) with 31 citations³⁹, and Tsokos GC (2016, Nat Rev Rheumatol) with 29 citations⁴⁰. The review by Tsokos GC (2016) published in Nature Reviews Rheumatology remains a cornerstone of the field and is widely cited for its overview of SLE pathogenesis⁴⁰. High-centrality references, which play critical bridging roles in the knowledge network, were also identified. Mohammadi S (2017, Lupus) exhibited the highest centrality (0.69)⁴¹, followed by Funes SC (2018, Immunology) (0.67)⁴². These references connect multiple research directions, linking basic immunological mechanisms, such as macrophage polarization and NLRP3 inflammasome activation, to clinical manifestations, such as lupus nephritis and cytokine storms (Figure 8A).

Cluster analysis identified 13 major thematic clusters, reflecting the core knowledge domains and research communities in the field. These clusters included #0 macrophage activation syndrome⁴³, #1 apoptosis, #2 hemophagocytic lymphohistiocytosis, #3 lactobacillus delbrueckii, #4 autoimmune diseases, #5 lupus nephritis, #6 peripheral blood mononuclear cells (PBMCs), #7 metabolism, #8 NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, #9 type I interferon, #10 dendritic cell, #11 cytokine storms, and #12 vitamin D. These clusters cover key research directions such as innate immune activation, inflammatory cell death, cytokine dysregulation, organ damage mechanisms, and therapeutic interventions, thereby providing the foundational framework for research on macrophages in SLE (Figure 8B).

Burst reference analysis revealed the dynamic evolution of the knowledge base in this field (Figure 8C). In terms of burst strength, the review by Tsokos GC (2016) had a burst strength of 10.45⁴⁴, with a burst period from 2018 to 2021, representing the most influential reference during this period. The study by Lood C (2016) exhibited a burst strength of 6.23, active from 2016 to 2020, highlighting the sustained impact of NETosis research. From a temporal perspective, burst references can be divided into three stages: 2016–2018, dominated by foundational reviews on SLE immunopathology and early mechanistic studies on macrophage dysfunction⁴⁴; 2019–2022, centered on advances in innate immunity, including studies on NLRP3 inflammasomes, dendritic cells, and apoptosis mechanisms^45,46, and 2023–2025, characterized by emerging research on cytokine storms, metabolism, and therapeutic interventions^47,48, reflecting a shift toward translational and clinical applications.

DATA AVAILABILITY:

The datasets generated and analyzed during this study are currently accessible through a Science Data Bank peer-review link: https://www.scidb.cn/en/detail?dataSetId=122808b00b8a4040a775db6bcc8d5a8a.

Figure 1: Schematic overview of the bibliometric workflow. The workflow comprises four main stages: literature retrieval from the Web of Science Core Collection; data screening and extraction; bibliometric analysis using CiteSpace and VOSviewer; and visualization and interpretation of the results. Abbreviation: WOSCC = Web of Science Core Collection. Please click here to view a larger version of this figure.

Figure 2: Annual publication volume and citation counts from 2016 to 2025. The bars represent the number of publications per year, and the line represents annual citation counts. Please click here to view a larger version of this figure.

Figure 3: Country/region bibliometric analysis. (A) Country/region collaboration network. Node size represents publication volume, node color denotes a collaboration cluster, and link thickness reflects collaboration intensity. (B) Chord diagram illustrating the strength and distribution of collaboration among major countries/regions. (C) Annual publication volume of the top 10 countries/regions from 2016 to 2025. Abbreviations: UK = United Kingdom; USA = United States of America. Please click here to view a larger version of this figure.

Figure 4: Institutional bibliometric analysis. (A) Institutional collaboration network. Node size represents publication volume, node color denotes a collaboration cluster, and link thickness reflects coauthorship intensity. (B) Top 10 institutions by publication volume with corresponding country/region affiliation. (C) Top 10 institutions by citation count with corresponding country/region affiliation. Abbreviations: NIAMSD = National Institute of Arthritis and Musculoskeletal and Skin Diseases; USA = United States of America. Please click here to view a larger version of this figure.

Figure 5: Journal bibliometric analysis. (A) Journal co-citation network. Node size represents publication volume, node color denotes a journal cluster, and link thickness reflects co-citation relationships. (B) Journal bubble chart. The x-axis represents citation counts, bubble size represents publication volume, and bubble color indicates impact factor. (C) Co-cited journal ranking. The x-axis represents citation counts, the y-axis lists journal names, and bar color indicates impact factor. Abbreviations: IF = impact factor; JCR = Journal Citation Reports. Please click here to view a larger version of this figure.

Figure 6: Author bibliometric analysis. (A) Author collaboration network. Node size represents publication volume, node color denotes a research cluster, and link thickness reflects coauthorship strength. (B) Ring chart of the top 10 authors by publication volume; segment size is proportional to publication count. (C) Top 10 authors by citation count with corresponding country/region affiliation. Abbreviation: USA = United States of America. Please click here to view a larger version of this figure.

Figure 7: Keyword bibliometric analysis. (A) Keyword co-occurrence network. Node size represents keyword frequency, node color denotes a thematic cluster, and link thickness reflects co-occurrence strength. (B) Top 25 keywords with the strongest citation bursts, ranked by burst strength; red bars indicate the burst period. (C) Keyword timeline visualization showing the evolution of research hotspots and emergence of new research directions from 2016 to 2025. Abbreviation: SLE = systemic lupus erythematosus. Please click here to view a larger version of this figure.

Figure 8: Reference bibliometric analysis. (A) Reference co-citation network. Node size represents citation frequency, node color denotes a reference cluster, and links reflect co-citation relationships. (B) Reference clustering map grouping co-cited references into thematic clusters based on shared citation patterns. (C) Top 15 references with the strongest citation bursts, ranked by burst strength; red bars indicate the burst period, and the blue line represents the study period. Abbreviations: NLRP3 = NOD-like receptor family pyrin domain-containing 3; PBMC = peripheral blood mononuclear cell. Please click here to view a larger version of this figure.

Rank	Country/region	Documents	Citations	Mean citations per paper	Total link strength
1	China	379	8935	24	77
2	USA	311	18838	61	178
3	Japan	74	1545	21	26
4	England	59	3902	66	78
5	Germany	57	3236	57	78
6	Italy	39	2177	56	38
7	Australia	38	1420	37	33
8	Sweden	33	2108	64	40
9	France	30	1417	47	40
10	South Korea	30	725	24	20

Table 1: Top 10 countries/regions by total publication volume. Countries/regions are sorted by publication volume.

Rank	Institution	Documents	Citations	Total link strength	Country/region
1	Shanghai Jiao Tong University	23	308	15	China
2	Karolinska Institutet	23	1929	18	Sweden
3	Sun Yat-sen University	21	821	26	China
4	Huazhong University of Science and Technology	20	384	11	China
5	Nanjing University	20	512	12	China
6	Chinese Academy of Sciences	18	855	27	China
7	Central South University	18	926	17	China
8	University of Washington	17	2095	9	USA
9	Nanjing Medical University	16	279	17	China
10	Harvard Medical School	16	1265	16	USA

Table 2: Top 10 institutions by total publication output. Institutions are sorted by publication volume.

Rank	Journal	Documents	Citations	Total link strength	IF	JCR quartile
1	Frontiers in Immunology	108	6104	221	5.9	Q1
2	Lupus	38	478	70	1.9	Q3
3	International Journal of Molecular Sciences	31	1028	47	4.9	Q1
4	Journal of Immunology	26	585	47	3.4	Q2
5	Arthritis & Rheumatology	24	911	56	10.9	Q1
6	Scientific Reports	23	526	20	3.9	Q1
7	Clinical Immunology	22	487	62	3.8	Q2
8	International Immunopharmacology	21	237	30	4.7	Q1
9	Journal of Autoimmunity	18	749	34	7.0	Q1
10	Autoimmunity Reviews	16	698	68	8.3	Q1

Table 3: Journal publication volume, impact factor, and quartile ranking. The table lists publication counts, impact factors, and Journal Citation Reports quartiles for the top 10 journals. Abbreviations: IF = impact factor; JCR = Journal Citation Reports.

Rank	Keyword (frequency)	Count	Keyword (centrality)	Centrality
1	systemic lupus erythematosus	666	autoimmune	0.31
2	expression	186	autoimmune diseases	0.30
3	activation	157	macrophage	0.30
4	rheumatoid arthritis	149	erythematosus	0.27
5	macrophages	144	mice	0.27
6	disease	112	atherosclerosis	0.26
7	macrophage activation syndrome	111	gene expression	0.25
8	dendritic cells	108	regulatory T cells	0.24
9	T cells	101	mouse model	0.24
10	cells	85	disease	0.23

Table 4: Top 10 keywords by frequency and betweenness centrality. High-frequency keywords indicate research hotspots, while high-betweenness-centrality keywords represent concepts that bridge multiple themes.

Discussion

This bibliometric study systematically delineates the research landscape of macrophages in SLE over the past decade (2016–2025). By analyzing 1,197 publications from the Web of Science Core Collection, we identified global publication trends, collaborative networks, core research forces, thematic evolution, and knowledge base dynamics, thereby providing an objective roadmap for future investigations in this rapidly evolving field.

Over the 10-year study period, annual publications on macrophages in SLE increased modestly from 112 in 2016 to a peak of 154 in 2022, then declined slightly to 133 in 2025. More importantly, annual citation counts increased overall from 184 to 9,030, indicating that despite fluctuations in output, the academic impact of this field has grown substantially. This growth trajectory aligns with the increasing recognition of macrophages as central players in SLE pathogenesis, beyond their traditional roles in immune complex clearance and efferocytosis. The past decade has witnessed landmark discoveries linking macrophage dysfunction to NETosis, type I interferon signatures, and metabolic reprogramming, which have catalyzed research interest^{49,50,51,52,53}. Notably, the peak in 2022 coincides with the publication of several high-impact mechanistic studies and the expansion of biologic therapies targeting innate immune pathways, suggesting that clinical translation has begun to drive basic research.

At the national level, China ranks first in publication volume, serving as the leading contributor worldwide, while the United States leads in total citations and international collaboration centrality. England, Sweden, and Germany, despite moderate publication volumes, exhibit the highest average citations per paper, reflecting their high citation impact. The country/region collaboration network formed three major clusters, with the United States and China appearing in the same major collaboration cluster as Mexico. Although China’s total link strength was moderate, its annual output has steadily increased from 18 to 70 articles over the decade, surpassing that of the United States after 2020. This shift may reflect China’s substantial investment in immunology research and growing collaborative capacity. The top 10 institutions by publication volume are predominantly in China, with domestic collaborations exhibiting distinct regional clustering, particularly among eastern institutions such as Shanghai Jiao Tong University, Sun Yat-sen University, and Huazhong University of Science and Technology. In contrast, the top 10 highly cited institutions are dominated by American and European institutions, such as the University of Washington, Karolinska Institutet, and Harvard Medical School, with NIAMSD achieving exceptionally high impact per paper. Journal analysis identified Frontiers in Immunology as the most productive journal, reflecting the open-access movement’s growing influence in immunology. High-impact subscription journals such as Nature Reviews Rheumatology and Arthritis & Rheumatology published fewer articles but accumulated substantial citations, underscoring their role in shaping the theoretical framework. The co-citation map highlighted Journal of Immunology as the most co-cited source, followed by Frontiers in Immunology and Lupus, illustrating the blend of classic immunology journals and specialty lupus journals that constitute the knowledge base. Author collaboration networks revealed five major clusters. Cluster 2, centered on Kaplan, M.J., Elkon, K.B., and Carmona-Rivera, C., focuses on NETs and efferocytosis—mechanisms that have reshaped our understanding of innate immune dysregulation in SLE^54,55. The high citation counts of Kaplan, Elkon, and Carmona-Rivera underscore the field’s growing recognition that defective clearance of dying cells and NET-mediated inflammation are not merely epiphenomena but central pathogenic drivers and therapeutic targets⁵⁶.

Keyword co-occurrence and timeline clustering analyses reveal that research themes in the field of macrophages in SLE exhibit prominent dynamic evolutionary characteristics. Early research predominantly focused on the fundamental mechanisms of macrophage dysfunction in SLE, with core emphases on macrophage polarization, apoptotic cell clearance, and immune complex handling. Through cluster analysis, 13 major thematic clusters were identified in this field. These multiple clusters systematically interpret the multifaceted regulatory roles of macrophages in innate immune activation, inflammatory cell death, cytokine dysregulation, multi-organ damage, and potential targeted therapeutic interventions. In the early research stage, scholars mainly concentrated on the basic physiological functions of macrophages, especially the clearance of apoptotic cells and circulating immune complexes, as well as the regulatory mechanism of autoimmune tolerance. The landmark discovery of impaired macrophage-mediated efferocytosis in SLE established a critical mechanistic link between macrophage functional defects and autoimmune disease progression⁵⁵. From 2019 to 2022, the research focus shifted to in-depth mechanistic exploration. Beyond abnormal cell clearance, macrophages were further recognized as core inflammatory amplifiers in SLE, driving persistent inflammatory responses via inflammasome activation and interferon-related positive feedback loops⁵⁶. Reference burst analysis verified that the landmark NETs research conducted by Lood C (2016) and the authoritative thematic review published by Tsokos GC (2016) maintained strong citation bursts during this period, which were highly consistent with the dynamically changing trend of core keywords in the same period. Meanwhile, metabolism gradually emerged and has attracted sustained attention, indicating that immunometabolic reprogramming of macrophages has become a rising research hotspot in this field. In recent years, the research frontiers of this field have been further updated and expanded, with emerging clusters such as cytokine storms, metabolism, and vitamin D, together with clinically oriented research directions. Among them, “pathway” and “multicenter diagnosis” have become cutting-edge research focuses, indicating that this field is gradually advancing toward targeted pathway therapy and standardized clinical diagnosis. Importantly, not all emerging keywords represent sustained research directions. When distinguishing between transient bursts and long-term trends, we observed that COVID-19-related terms appeared as short-lived phenomena, likely reflecting the temporary research surge during the global pandemic period. In contrast, topics such as macrophage polarization, metabolic reprogramming, and targeted therapy have demonstrated more consistent and lasting traction across the study period, indicating they represent genuine, sustained research frontiers rather than ephemeral hotspots. The high-burst keywords in the latest stage mainly include cytokine storm, metabolic reprogramming, vitamin D, macrophage polarization, and therapeutic target, which fully reflect the latest research priorities. In addition, two emerging exploratory directions have gained attention. One is Lactobacillus delbrueckii, which reflects a growing interest in gut microbiome regulation in SLE⁵⁷. The other is peripheral blood mononuclear cell (PBMC) molecular signatures, which provide novel noninvasive biomarker ideas for auxiliary diagnosis and condition evaluation of SLE⁵⁸. Notably, lupus nephritis has remained a persistent research hotspot across all evolutionary stages, fully demonstrating that renal injury, as the most common severe organ complication of SLE, is still the core clinical challenge driving in-depth research on macrophages⁵⁹. Vitamin D and metabolic reprogramming exhibit high citation-burst intensity, marking them as the most dynamic and promising emerging frontiers in the current research landscape.

Although systematic systems biology research has not yet yielded independent clustering topics in this field, emerging technologies such as single-cell RNA sequencing, multi-omics, and machine learning have been widely applied in high-quality, high-impact publications. Single-cell transcriptomics technology has successfully identified multiple functionally defective macrophage subsets in SLE patients, such as MerTK⁺ phagocytic macrophages, providing a basis for further investigation of disease mechanisms and therapeutic targets for in-depth exploration of disease mechanisms^60,61,62,63. The integration of single-cell sequencing, spatial transcriptomics, and other advanced cutting-edge technologies brings new perspectives for revealing the complex pathogenesis of autoimmune injury^64,65,66. Reference co-citation analysis further confirms that this field possesses a complete and structured knowledge base. Milestone studies represented by Tsokos GC (2016, Nature Reviews Rheumatology) and Lood C (2016, Nature Medicine) constitute the core theoretical framework of this research domain. Citation burst analysis clearly divides the evolution of the knowledge system into three progressive stages, intuitively reflecting the continuous deepening and innovation of research content in this field.

Despite these advances, several challenges remain. Macrophage heterogeneity in SLE is still poorly characterized. Single-cell RNA sequencing has revealed unexpected subsets, such as the MerTK+ phagocytic macrophages that are defective in SLE patients⁶⁷. How these subsets differentially contribute to disease initiation, flares, and organ damage requires further investigation^68,69. Although targeting macrophages holds therapeutic promise—for example, promoting efferocytosis via peroxisome proliferator-activated receptor gamma (PPARγ) agonists, inhibiting NLRP3 inflammasome with MCC950, or skewing polarization toward M2 phenotypes—most interventions remain preclinical. High-quality, multicenter randomized controlled trials are urgently needed to evaluate macrophage-targeted therapies in SLE. The translation of multi-omics signatures into clinically actionable biomarkers and treatment algorithms remains a gap. Future research should integrate systems biology approaches with rigorous clinical phenotyping to achieve precision medicine for SLE.

This study has several limitations that should be acknowledged. First, the data were sourced exclusively from the Web of Science Core Collection, excluding other databases such as PubMed, Scopus, or Chinese databases (CNKI, Wanfang). This may have introduced selection bias, particularly for regionally significant studies. While WOSCC is widely used for bibliometric analysis, and our findings are generally consistent with previous studies that also relied primarily on WOSCC, inclusion of additional databases such as Scopus or PubMed might have captured a broader range of publications and potentially altered the observed collaboration patterns. Second, our search was restricted to English-language publications, which may have underrepresented important contributions published in other languages, particularly from non-English-speaking countries with active SLE research programs. Third, bibliometric analysis describes external characteristics and co-occurrence relationships but cannot assess the quality, innovation, or clinical validity of individual studies. Fourth, the 2016–2025 timeframe was chosen to capture the most recent decade; however, some foundational work published before 2016 is inevitably underrepresented in burst detection. Fifth, citation-based indicators inherently suffer from citation lag, meaning that recently published high-quality studies may have accumulated fewer citations simply because they have not had sufficient time to accrue citations, potentially underestimating their true impact. This temporal bias is particularly relevant for 2025 publications included in our analysis. Finally, we acknowledge that our analysis did not specifically account for potential retractions. Our dataset was derived from the Web of Science Core Collection, which does not automatically exclude retracted articles. Because the analysis did not identify or quantify retracted records, the extent of their influence on aggregate bibliometric patterns is unknown.

In conclusion, this bibliometric analysis provides a comprehensive and objective mapping of the macrophages in the SLE field. The results demonstrate a dynamic evolution from basic immunological observations to detailed mechanistic inquiries and, more recently, to translational and clinical applications. China has emerged as the largest contributor by volume, whereas the United States and European countries continue to lead in impact and collaboration centrality. The knowledge base is anchored by landmark reviews and mechanistic studies on NETosis, type I interferon, and efferocytosis. Current frontiers center on cytokine storms, immunometabolism, and pathway-targeted therapies, with “multicenter diagnosis” and “type I interferon pathways” representing the most vibrant research fronts. Beyond summarizing our current findings, this study proposes several specific applications of bibliometric analysis for guiding future SLE research. First, we have identified sustained research directions, particularly macrophage polarization, metabolic reprogramming, and targeted therapy. These areas provide evidence-based guidance to help funding agencies prioritize resource allocation toward fields that have demonstrated long-term scientific traction. Second, the underrepresentation of clinical trial publications and the scarcity of multicenter validation studies revealed in our analysis highlight critical research gaps that warrant targeted investment. Third, the observed collaborative networks are largely concentrated within China and the United States, while cross-cluster connections with other regions remain relatively sparse. This pattern suggests opportunities for facilitating international collaborative initiatives, especially among research centers in Asia, Europe, and Latin America, to accelerate global progress in macrophage-targeted SLE therapies. Future efforts should prioritize international collaboration, high-quality clinical trials, and the integration of multi-omics approaches to translate macrophage biology into tangible benefits for SLE patients.

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
CiteSpace (version 6.4.R1)	Drexel University, Philadelphia, PA, USA	N/A	Keyword timeline clustering and citation burst analysis; RRID: SCR_020932; URL: https://citespace.podia.com
GraphPad Prism (version 10.1)	Dotmatics, Boston, MA, USA	N/A	Figure preparation and data visualization; RRID: SCR_002798; URL: https://www.graphpad.com
Scimago Graphica (version 1.0.25)	Scimago Lab, Madrid, Spain	N/A	Country/region collaboration network visualization; RRID: not available; URL: https://www.graphica.app
VOSviewer (version 1.6.19)	Centre for Science and Technology Studies, Leiden University, Leiden, Netherlands	N/A	Coauthorship network construction and keyword co-occurrence mapping; RRID: SCR_016598; URL: https://www.vosviewer.com
Web of Science Core Collection	Clarivate Analytics, Philadelphia, PA, USA	N/A	Literature retrieval and data source; URL: https://clarivate.com/webofscience
WPS Excel (2023)	Kingsoft, Zhuhai, China	N/A	Basic statistical calculations and bar, line, and pie charts; RRID: not available; URL: https://www.wps.com