Mutations of the gene encoding the cytoplasmic phosphatase PTPN22 confer an increased risk of autoimmunity in humans and mice, and this is associated with increased numbers of B and T cells. However Ptpn22−/− mice do not spontaneously develop autoimmunity. This study shows that such mice have an increased number of regulatory T (TReg) cells with increased immunosuppressive activity, which can prevent autoimmunity caused by Ptpn22−/− effector T cells in a mouse colitis model. Ptpn22−/− TReg cells secreted higher levels of interleukin-10 (IL-10) than wild-type TReg cells and had increased integrin-mediated adhesion downstream of T cell receptor signalling, both of which are crucial for TReg cell function. Therefore, PTPN22 regulates both effector and regulatory T cell populations to maintain homeostasis.
ORIGINAL RESEARCH PAPER
Brownlie, R. J. et al. Lack of the phosphatase PTPN22 increases adhesion of murine regulatory T cells to improve their immunosuppressive function. Sci. Signal. 5, ra87 (2012)
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Minton, K. The role of PTPN22 in T cell homeostasis. Nat Rev Immunol 13, 6 (2013). https://doi.org/10.1038/nri3374
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DOI: https://doi.org/10.1038/nri3374