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PTPN22 alters the development of regulatory T cells in the thymus.

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.

SUBMITTER: Maine CJ

PROVIDER: S-EPMC3358490 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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PTPN22 alters the development of regulatory T cells in the thymus.

Maine Christian J CJ Hamilton-Williams Emma E EE Cheung Jocelyn J Stanford Stephanie M SM Bottini Nunzio N Wicker Linda S LS Sherman Linda A LA

Journal of immunology (Baltimore, Md. : 1950) 20120425 11

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 pers ...[more]

PMID: 22539785

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