PTPN22 alters the development of regulatory T cells in the thymus |
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Authors: | Maine Christian J Hamilton-Williams Emma E Cheung Jocelyn Stanford Stephanie M Bottini Nunzio Wicker Linda S Sherman Linda A |
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Institution: | Department of Immunology and Microbial Sciences, The Scripps Research Institute, La Jolla, CA 92037, USA. |
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Abstract: | PTPN22 encodes a tyrosine phosphatase that inhibits Src-family kinases responsible for Ag receptor signaling in lymphocytes and is strongly linked with susceptibility to a number of autoimmune diseases. As strength of TCR signal is critical to the thymic selection of regulatory T cells (Tregs), we examined the effect of murine PTPN22 deficiency on Treg development and function. In the thymus, numbers of pre-Tregs and Tregs increased inversely with the level of PTPN22. This increase in Tregs persisted in the periphery and could play a key part in the reduced severity observed in the PTPN22-deficient mice of experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis. This could explain the lack of association of certain autoimmune conditions with PTPN22 risk alleles. |
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