examination-oral-candida-infection-primary-sjgren-s-syndrome

Examination of Oral <i>Candida</i> Infection in Primary Sj&#246;gren&#39;s Syndrome Patients

Primary Sj&#246;gren's syndrome (pSS) is an autoimmune disease characterized by symptoms such as dry mouth, dry eyes, and other systematic symptoms. Due ...

Capital Medical University

Sjögren's syndrome (SS) is characterized by autoimmune activation and loss of function in the salivary glands. Recent studies reported that bone morphogenetic protein 6 (BMP6), which is a member of transforming growth factor beta (TGF-β) superfamily, was highly expressed in SS patients. To investigate the role of BMP6 in SS, we treated the salivary gland-derived mesenchymal stem cells (SGMSCs) with BMP6 and found that BMP6 could impair immunomodulatory properties of normal SGMSCs by downregulating the Prostaglandin E2 synthase through DNA-binding protein inhibitor-1. Neutralizing the BMP6 could significantly restore the SGMSC's immunoregulatory function in vitro and delay the SS disease activity in vivo. In conclusion, BMP6 could not only affect the secreting function of epithelial cells in the salivary gland but also influence the immunomodulatory properties of SGMSCs, which may trigger or enhance the autoimmune reflection in SS.

Effect of Bone Morphogenetic Protein 6 on Immunomodulatory Functions of Salivary Gland-Derived Mesenchymal Stem Cells in Sjögren's Syndrome.

Mesenchymal stem cells (MSCs) treatment has emerged as a promising approach for treating Sjögren's syndrome (SS). Impaired immunoregulatory activities of bone marrow mesenchymal stem cells (BMMSCs) are found in both SS patients and animal models, and the underlying mechanism is poorly understood. Increased expression of BMP6 is reported to be related to SS. The aim herein was to determine the effects of BMP6 on BMMSCs function. BMMSCs were isolated from SS patients and NOD mice and showed a high level of BMP6 expression. The effects of BMP6 on BMMSCs function were investigated using  BMMSCs differentiation and  and  T cell proliferation and polarization assays. BMP6 increased osteogenic differentiation of BMMSCs and inhibited the immunomodulatory properties of BMMSCs. BMP6 enhanced T cell proliferation and Th1/Th17 differentiation in a T cell-BMMSC coculture system. Mechanistically, BMP6 downregulated PGE2 and upregulated IFN-gamma via Id1 (inhibitor of DNA-binding protein 1). Neutralizing BMP6 and knockdown of Id1 could restore the BMMSCs immunosuppressive function both  and . The present results suggest a novel role of Id1 in BMP-mediated MSCs function, which may contribute to a better understanding of the mechanism of action of MSCs in treating autoimmune diseases.

Bone Morphogenetic Protein 6 Inhibits the Immunomodulatory Property of BMMSCs via Id1 in Sjögren's Syndrome.

TCRαβCD8αα intraepithelial lymphocytes (IELs) are abundant in gastrointestinal (GI) tract and play an important role in regulation of mucosal immunity and tolerance in the gut. However, it is unknown whether TCRαβCD8αα IELs exist in the oral mucosa and if yes, what controls their development. We here identified and characterized TCRαβCD8αα IELs from the murine oral mucosa. We showed that the number and function of TCRαβCD8αα IELs were regulated by TGF-β. We further revealed that oral TCRαβCD8αα IELs could be altered under systemic inflammatory conditions and by antibiotic treatment at the neonatal age of the mice. Our findings have revealed a previously unrecognized population of oral IELs that may regulate oral mucosal immune responses.

Identification and Regulation of TCRαβCD8αα Intraepithelial Lymphocytes in Murine Oral Mucosa.

CD4 T cells are the key to many immune-inflammatory diseases mediated by microbial disorders, especially inflammatory bowel disease (IBD). The purpose of this study was to explore how pathogenic and probiotic bacteria directly affect the T helper (Th)17 and T regulatory (Treg) cell balance among CD4 T cells to regulate inflammation.

Article	Year
Effect of Bone Morphogenetic Protein 6 on Immunomodulatory Functions of Salivary Gland-Derived Mesenchymal Stem Cells in Sjögren's Syndrome. Stem cells and development\| PubMed ID: 30132383	2018
Bone Morphogenetic Protein 6 Inhibits the Immunomodulatory Property of BMMSCs via Id1 in Sjögren's Syndrome. Stem cells international\| PubMed ID: 30174696	2018
Identification and Regulation of TCRαβCD8αα Intraepithelial Lymphocytes in Murine Oral Mucosa. Frontiers in immunology\| PubMed ID: 32849598	2020
and GG regulate the Th17/Treg balance in colitis via TLR4 and TLR2. Clinical & translational immunology\| PubMed ID: 33282294	2020

Ruiqing Wu

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