title: 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.
authors.affiliation: Department of Immunology and Microbial Sciences, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Maine
authors.forename: Emma E
authors.initials: EE
authors.lastname: Hamilton-Williams
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Cheung
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Stanford
authors.forename: Nunzio
authors.initials: N
authors.lastname: Bottini
authors.forename: Linda S
authors.initials: LS
authors.lastname: Wicker
authors.forename: Linda A
authors.initials: LA
authors.lastname: Sherman
mesh_terms: D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000201:enzymology* / Q000276:immunology* / Q000473:pathology; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009103:Multiple Sclerosis / Q000276:immunology / Q000473:pathology; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000201:enzymology* / Q000276:immunology* / Q000473:pathology; D013950:Thymus Gland / Q000201:enzymology* / Q000276:immunology* / Q000473:pathology; D015854:Up-Regulation / Q000276:immunology
chemical_list: D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; C516766:Ptpn22 protein, mouse