%0 Journal Article
%T Interleukin-10 produced by B cells is crucial for the suppression of Th17/Th1 responses, induction of T regulatory type 1 cells and reduction of collagen-induced arthritis
%A Natalie A Carter
%A Elizabeth C Rosser
%A Claudia Mauri
%J Arthritis Research & Therapy
%D 2012
%I BioMed Central
%R 10.1186/ar3736
%X We 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.Here 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.IL-10 producing B cells restrain inflammation by promoting differentiation of immuno-regulatory over pro-inflammatory T cells and, hence, act to maintain tolerance.CIA-induced joint destruction is widely accepted to develop as a result of the secretion of pro-inflammatory Th1 cytokines, such as IFN¦Ã and IL-12 [1-3]. These Th1 cytokines facilitate the infiltration of neutrophils and macrophages into the joint, which stimulates the production of both TNF¦Á and IL-1 that ultimately results in joint destruction and pannus formation [4,5]. In addition to this, 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 (¦ÌMT) are resistant to CIA [8] shows that CIA is both a T and B cell-mediated disease.The role of IL-10 has been well documented in experimental arthritis [9-13] and other autoimmune disorders [14-18]. It has been shown that CIA is exacerbated in IL-10 deficient DBA mice [12], although the relevant contributions of IL-10 secreted by T cells and B cells cannot be revealed using IL-10-/- animals. The importance of B cell derived IL-10 in CIA has been confirmed by previous work in this laboratory [9,10]. Several regulatory B cell subsets have now been identified and most share the release of IL-10 as a common mechanism of act
%U http://arthritis-research.com/content/14/1/R32