Abstract
IntroductionInterleukin-10 (IL-10) producing B cells, also known as regulatory B (Breg) cells, play a key role in controlling autoimmunity. Our laboratory and others have demonstrated a pivotal role for Bregs in rheumatological disorders, including experimental models of arthritis and lupus. The aim of this study was to identify the role of endogenous IL-10 secreting B cells in vivo in controlling the induction and disease progression of collagen-induced arthritis (CIA).MethodsWe generated chimeric mice that had IL-10 knocked-out specifically in the B cell population. These mice were compared with wild-type (WT) B cell chimeric mice for their susceptibility to CIA.ResultsHere we report that chimeric mice specifically lacking IL-10 producing B cells (IL-10-/- B cell) developed an exacerbated CIA compared to chimeric wild type B cell (WT B cell) mice. A marked increase in inflammatory Th1 and Th17 cells were detected in IL-10-/-B cell mice compared to WT B cell mice. Furthermore, there was a reduction in IL-10 secreting CD4+ Tr1 cells in these animals.ConclusionsIL-10 producing B cells restrain inflammation by promoting differentiation of immuno-regulatory over pro-inflammatory T cells and, hence, act to maintain tolerance.
Highlights
Interleukin-10 (IL-10) producing B cells, known as regulatory B (Breg) cells, play a key role in controlling autoimmunity
We have shown that the transfer of the main producers of IL-10, namely CD19+CD21hiCD23hiCD1dhi transitional 2 marginal zone precursor B cells (T2-MZP), prevents or ameliorates established disease [9,19]
IL-10 is essential for the regulation of experimental arthritis It is well documented that mice lacking IL-10 have a predisposition to immune-driven colitis and inflammation of the gut [16,30,31]
Summary
Interleukin-10 (IL-10) producing B cells, known as regulatory B (Breg) cells, play a key role in controlling autoimmunity. The aim of this study was to identify the role of endogenous IL-10 secreting B cells in vivo in controlling the induction and disease progression of collagen-induced arthritis (CIA). CIA is mediated by pathogenic B cells, which produce anti-collagen antibodies that are indicative of disease development [5] and can induce arthritis upon transfer [6,7]. This taken together with the fact that B cell deficient mice (μMT) are resistant to CIA [8] shows that CIA is both a T and B cell-mediated disease. Providing us with a unique environment to assess the role of B cell derived IL-10 in joint inflammation
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