Where FoxP3‐dependent regulatory T cells impinge on the development of inflammatory arthritis
- 30 January 2007
- journal article
- Published by Wiley in Arthritis & Rheumatism
- Vol. 56 (2), 509-520
- https://doi.org/10.1002/art.22272
Abstract
Objective Regulatory T cells play a suppressive role in many autoimmune diseases and can potentially affect various steps in the progression of disease. The purpose of this study was to analyze the role of Treg cells in the control of arthritis development. Methods Using crosses and cell transfers, we tested the effect of the scurfy loss‐of‐function mutation of the Foxp3 gene in the K/BxN mouse model. In this model, arthritis develops as the result of the production of high levels of pathogenic autoantibodies. Results The absence of Treg cells in K/BxN mice led to faster and more aggressive arthritis. Strikingly, disease also spread to joints not normally affected in this model. The absence of Treg cells resulted in an acceleration of the immunologic phase of disease, with significantly earlier autoantibody production. However, the broadened spectrum of affected joints in Foxp3‐mutant mice was not due to the earlier appearance of autoantibodies and could not be reproduced by increasing the anti–glucose‐6‐phosphate isomerase antibody load, which demonstrates an impact of Treg cells on effector phase manifestations. In addition, FoxP3+,CD25+ Treg cells accumulated in inflamed joints, even in nontransgenic animals. This preferential localization mimics that in human arthritides and indicates a preferential homing/retention of Treg cells to sites of inflammation. Conclusion These results indicate that Treg cells play a role in antibody‐mediated arthritis at several levels. Treg cells are involved in constraining the immune phase of disease, as well as limiting the articular damage provoked by the pathogenic autoantibodies in terms of severity and of the range of affected joints, which may contribute to the limited distal predominance of many arthritides.Keywords
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