Lack of the Phosphatase PTPN22 Increases Adhesion of Murine Regulatory T Cells to Improve Their Immunosuppressive Function
- 27 November 2012
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Signaling
- Vol. 5 (252), ra87
- https://doi.org/10.1126/scisignal.2003365
Abstract
The cytoplasmic phosphatase PTPN22 (protein tyrosine phosphatase nonreceptor type 22) plays a key role in regulating lymphocyte homeostasis, which ensures that the total number of lymphocytes in the periphery remains relatively constant. Mutations in PTPN22 confer an increased risk of developing autoimmune diseases; however, the precise function of PTPN22 and how mutations contribute to autoimmunity remain controversial. Loss-of-function mutations in PTPN22 are associated with increased numbers of effector T cells and autoreactive B cells in humans and mice; however, the complete absence of PTPN22 in mice does not result in spontaneous autoimmunity. We found that PTPN22 was a key regulator of regulatory T cell (Treg) function that fine-tuned the signaling of the T cell receptor and integrins. PTPN22−/− Tregs were more effective at immunosuppression than were wild-type Tregs, and they suppressed the activity of PTPN22−/− effector T cells, preventing autoimmunity. Compared to wild-type Tregs, PTPN22−/− Tregs produced increased amounts of the immunosuppressive cytokine interleukin-10 and had enhanced adhesive properties mediated by the integrin lymphocyte function–associated antigen-1, processes that are critical for Treg function. This previously undiscovered role of PTPN22 in regulating integrin signaling and Treg function suggests that PTPN22 may be a useful therapeutic target for manipulating Treg function in human disease.Keywords
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