CD11b regulates the Treg/Th17 balance in murine arthritis via IL-6
JournalEuropean Journal of Immunology
MetadataShow full item record
AbstractTh17 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). 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. Copyright 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
SponsorsThe work was supported by grants from the Swiss National Science Foundation to HAO.
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85015196794&doi=10.1002%2feji.201646565&partnerID=40&md5=5b2a0d6c789dce827d7b3deb723608ff; http://hdl.handle.net/10713/10031
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