Altered peripheral B lymphocyte homeostasis and functions mediated by IL-27 via activating the mammalian target of rapamycin signaling pathway in patients with rheumatoid arthritis.
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| Abstract |
B cell dysfunction and inflammatory cytokine over-production participate in the pathogenesis of rheumatoid arthritis (RA). Here we compared peripheral B cell homeostasis and immune functions between RA patients and healthy controls (HC) and explored vital signaling pathways involved in altered RA B cells. We found that RA patients showed significantly decreased frequencies of peripheral CD19+ CD27+ CD24high regulatory B (Breg) cells but increased frequencies of CD19+ CD27+ CD38high plasmablasts and CD19+ CD138+ plasma cells, and higher levels of serum immunoglobulin (Ig)M and IgG. Compared to HC peripheral B cells, RA peripheral B cells had more increased proliferation and higher expression of activation markers. Importantly, our results showed that RA peripheral B cells displayed the mTOR signaling pathway to be more activated, and inhibition of mTOR could restore RA B cell homeostasis and functions. RA serum-treated B cells exhibited more increased expressions of mTOR, which could be restored with the addition of anti-interleukin (IL)-27 neutralizing antibody. Serum IL-27 levels were significantly increased in RA patients and positively correlated with disease activity, the frequencies of plasma cells and the levels of autoantibodies. In vitro, IL-27 notably promoted immune dysfunction of RA B cells, which were inhibited by anti-IL-27 neutralizing antibody. Also, the mTOR pathway was more activated in IL-27-treated RA B cells, and mTOR inhibition apparently reversed abnormalities of RA B cells mediated by IL-27. These results suggest that increased serum IL-27 levels could promote peripheral B cell dysfunction in RA patients via activating the mTOR signaling pathway. Thus, IL-27 may play a pro-pathogenic role in the development of RA, and antagonizing IL-27 could be a novel therapy strategy for RA.
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| Authors | Yawei Tang, Ziran Bai, Jingjing Qi, Zhimin Lu, Ahmad, Guan Wang, Minli Jin, Bing Wang, Haifeng Chen, Xia Li |
| Journal | Clinical and experimental immunology (Clin Exp Immunol) Vol. 206 Issue 3 Pg. 354-365 (12 2021) ISSN: 1365-2249 [Electronic] England |
| PMID | 34558072 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | © 2021 British Society for Immunology. |
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