Open AccessPTPN22 Alters the Development of Regulatory T Cells in the Thymus
Author(s) -
Christian J. Maine,
Emma E. HamiltonWilliams,
Jocelyn Cheung,
Stephanie M. Stanford,
Nunzio Bottini,
Linda S. Wicker,
Linda A. Sherman
Publication year - 2012
Publication title -
the journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.737
H-Index - 372
eISSN - 1550-6606
pISSN - 0022-1767
DOI - 10.4049/jimmunol.1200150
Subject(s) - ptpn22 , protein tyrosine phosphatase , experimental autoimmune encephalomyelitis , t cell receptor , immunology , thymectomy , biology , phosphatase , proto oncogene tyrosine protein kinase src , kinase , microbiology and biotechnology , t cell , multiple sclerosis , myasthenia gravis , phosphorylation , genetics , gene , genotype , immune system , single nucleotide polymorphism
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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