Altered peripheral B lymphocyte homeostasis and functions mediated by IL-27 via activating the mTOR signaling pathway in patients with rheumatoid arthritis

Clin Exp Immunol. 2021 Sep 24. doi: 10.1111/cei.13663. Online ahead of print.ABSTRACTB cell dysfunction and inflammatory cytokines 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, whereas increased frequencies of CD19+ CD27+ CD38high plasmablasts and CD19+ CD138+ plasma cells, and higher levels of serum IgM and IgG. Compared to HC peripheral B cells, RA peripheral B cells had more increased proliferation and higher expressions of activation markers. Importantly, our results showed that RA peripheral B cells displayed more activated the mTOR signaling pathway, 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-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 auto-antibodies. In vitro, IL-27 notably promoted immune dysfunction of RA B cells, which were inhibited by anti-IL-27 neutralizing antibody. Besides, the mTOR pathway was more activated in IL-27-treated...
Source: Clinical and Developmental Immunology - Category: Allergy & Immunology Authors: Source Type: research