mendelian-randomization-bioinformatics-identify-ifi27-as-candidate

Mendelian Randomization and Bioinformatics Identify IFI27 as a Candidate Biomarker for Recurrent Pregnancy Loss in Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is associated with adverse pregnancy outcomes, but its causal relationship with recurrent pregnancy loss (RPL) and ...

China Academy Of Chinese Medical Sciences

Recent studies have demonstrated a central role for plasma cells in the development of autoimmune diseases, such as systemic lupus erythematosus (SLE). Currently, both the phenotypic features and functional regulation of autoreactive plasma cells during SLE pathogenesis remain largely unclear. In this study, we first found that a major subset of IL-17 receptor-expressing plasma cells potently produced anti-dsDNA IgG upon IL-17A (IL-17) stimulation in SLE patients and lupus mice. Using a humanized lupus mouse model, we showed that the transfer of Th17 cell-depleted PBMCs from lupus patients resulted in a significantly reduced plasma cell response and attenuated renal damage in recipient mice compared to the transfer of total SLE PBMCs. Moreover, long-term BrdU incorporation in lupus mice detected highly enriched long-lived BrdU subsets among IL-17 receptor-expressing plasma cells. Lupus mice deficient in IL-17 or IL-17 receptor C (IL-17RC) exhibited a diminished plasma cell response and reduced autoantibody production with attenuated renal damage, while the adoptive transfer of Th17 cells triggered the plasma cell response and renal damage in IL-17-deficient lupus mice. In reconstituted chimeric mice, IL-17RC deficiency resulted in severely impaired plasma cell generation but showed no obvious effect on germinal center B cells. Further mechanistic studies revealed that IL-17 significantly promoted plasma cell survival via p38-mediated Bcl-xL transcript stabilization. Together, our findings identified a novel function of IL-17 in enhancing plasma cell survival for autoantibody production in lupus pathogenesis, which may provide new therapeutic strategies for the treatment of SLE.

IL-17 sustains the plasma cell response via p38-mediated Bcl-xL RNA stability in lupus pathogenesis.

This study aims to determine a role of interleukin-17A (IL-17) in salivary gland (SG) dysfunction and therapeutic effects of targeting IL-17 in SG for treating autoimmune sialadenitis in primary Sjögren's syndrome (pSS).

Article	Year
IL-17 sustains the plasma cell response via p38-mediated Bcl-xL RNA stability in lupus pathogenesis. Cellular & molecular immunology\| PubMed ID: 32917979	2021
IL-17 drives salivary gland dysfunction via inhibiting TRPC1-mediated calcium movement in Sjögren's syndrome. Clinical & translational immunology\| PubMed ID: 33968407	2021

Quan Jiang

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