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Mast cell promotion of T cell-driven antigen-induced arthritis despite being dispensable for antibody-induced arthritis in which T cells are bypassed.
Arthritis Rheum. 67, 903-913 (2015)
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OBJECTIVE: The function of mast cells (MCs) in autoimmune disorders has been a subject of controversy recently. MC-deficient Kit(W/W-v) mice were found to be resistant to K/BxN serum-transfer arthritis, whereas Kit(W-sh/W-sh) mice and a genetic model of MC deficiency independent of the Kit mutation were found to be fully susceptible. This debate might lead to the assumption that MCs are dispensable in autoimmunity in general. Thus, the purpose of this study was to examine the relevance of MCs to arthritis using a genetic model of inducible MC deficiency without compromised Kit signaling. METHODS: We compared MC functions in K/BxN serum-induced arthritis and in collagen-induced arthritis (CIA) in a mouse model of inducible MC deficiency by analyzing joint inflammation, parameters of cartilage degradation and bone erosion, and the autoreactive adaptive immune response. RESULTS: We observed a redundant role of MCs in K/BxN serum-induced arthritis, where joint inflammation is triggered by cartilage-bound immune complexes independently of T cells. In contrast, we found MCs to be critically relevant in CIA, which is provoked by two arms of autoimmune attack: autoreactive antibodies and effector T cells. In addition to diminished joint inflammation in the absence of MCs, we found a dramatic loss of T cell expansion upon immunization, accompanied by reduced T cell cytokine responses. CONCLUSION: In this analysis of an arthritis model in which the cellular arm of adaptive immunity was not bypassed, we identified MCs as important promoters of T cell-conditioned autoimmune disorders and, consequently, as potential therapeutic targets in rheumatoid arthritis.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
ISSN (print) / ISBN 0004-3591
Zeitschrift Arthritis & Rheumatology
Quellenangaben Band: 67, Heft: 4, Seiten: 903-913
Institut(e) Institute for Pancreatic Beta Cell Research (IPI)