Mast Cell Promotion of T Cell–Driven Antigen‐Induced Arthritis Despite Being Dispensable for Antibody‐Induced Arthritis in Which T Cells Are Bypassed

N Schubert, J Dudeck, P Liu, A Karutz… - Arthritis & …, 2015 - Wiley Online Library
N Schubert, J Dudeck, P Liu, A Karutz, S Speier, M Maurer, J Tuckermann, A Dudeck
Arthritis & rheumatology, 2015Wiley Online Library
Objective The function of mast cells (MCs) in autoimmune disorders has been a subject of
controversy recently. MC‐deficient KitW/W‐v mice were found to be resistant to K/BxN serum–
transfer arthritis, whereas KitW‐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 …
Objective
The function of mast cells (MCs) in autoimmune disorders has been a subject of controversy recently. MC‐deficient KitW/W‐v mice were found to be resistant to K/BxN serum–transfer arthritis, whereas KitW‐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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