CD11b regulates via IL-6 the Treg/Th17 balance in murine arthritis

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  • This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/eji.201646565

Abstract

Th17 cells are often associated with autoimmunity and been shown to be increased in CD11b−/- mice. Here, we examined the role of CD11b in murine collagen-induced arthritis (CIA)-induced arthritis. C57BL/6 and CD11b−/− resistant mice were immunized with type II collagen. CD11b−/- mice developed arthritis with early onset, high incidence and sustained severity compared with C57BL/6 mice. We observed a marked leukocyte infiltration, and histological examinations of the arthritic paws from CD11b−/− mice revealed that the cartilage was destroyed in association with strong lymphocytic infiltration. The CD11b deficiency led to enhanced Th17-cell differentiation. CD11b−/- dendritic cells (DCs) induced much stronger IL-6 production and hence Th17-cell differentiation than wild type DCs. Treatment of CD11b−/− mice after establishment of the Treg/Th17 balance with an anti-IL-6 receptor mAb significantly suppressed the induction of Th17 cells and reduced arthritis severity. Finally, the severe phenotype of arthritis in CD11b−/− mice was rescued by adoptive transfer of CD11b+ DCs. Taken together, our results indicate that the resistance to CIA in C57BL/6 mice is regulated by CD11b via suppression of IL-6 production leading to reduced Th17-cell differentiation. Therefore, CD11b may represent a susceptibility factor for autoimmunity and could be a target for future therapy.

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