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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Encephalomyelitis, Autoimmune, Experimental / enzymology*
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Encephalomyelitis, Autoimmune, Experimental / immunology*
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Encephalomyelitis, Autoimmune, Experimental / pathology
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Female
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Multiple Sclerosis / immunology
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Multiple Sclerosis / pathology
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Protein Tyrosine Phosphatase, Non-Receptor Type 22 / biosynthesis
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Protein Tyrosine Phosphatase, Non-Receptor Type 22 / deficiency
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Protein Tyrosine Phosphatase, Non-Receptor Type 22 / physiology*
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T-Lymphocytes, Regulatory / enzymology*
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T-Lymphocytes, Regulatory / immunology*
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T-Lymphocytes, Regulatory / pathology
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Thymus Gland / enzymology*
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Thymus Gland / immunology*
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Thymus Gland / pathology
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Up-Regulation / immunology
Substances
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Protein Tyrosine Phosphatase, Non-Receptor Type 22
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Ptpn22 protein, mouse