title: Multifunctional roles of the autoimmune disease-associated tyrosine phosphatase PTPN22 in regulating T cell homeostasis.
abstract: The non-receptor tyrosine phosphatase PTPN22 has a vital function in inhibiting antigen-receptor signaling in T cells, while polymorphisms in the PTPN22 gene are important risk alleles in human autoimmune diseases. We recently reported that a key physiological function of PTPN22 was to prevent naïve T cell activation and effector cell responses in response to low affinity antigens. PTPN22 also has a more general role in limiting T cell receptor-induced proliferation. Here we present new data emphasizing this dual function for PTPN22 in T cells. Furthermore, we show that T cell activation modulates the expression of PTPN22 and additional inhibitory phosphatases. We discuss the implication of these findings for our understanding of the roles of PTPN22 in regulating T cell responses and in autoimmunity.
authors.affiliation: a Institute of Immunology and Infection Research ; Ashworth Laboratories ; University of Edinburgh ; Edinburgh , UK.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Salmond
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Brownlie
authors.forename: Rose
authors.initials: R
authors.lastname: Zamoyska
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000201:enzymology* / Q000276:immunology*; D049109:Cell Proliferation; D006706:Homeostasis; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008231:Lymphopenia / Q000276:immunology; D051379:Mice; D023421:Models, Animal; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D015854:Up-Regulation
chemical_list: D000941:Antigens; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; C516766:Ptpn22 protein, mouse
keywords: Ag; LIP; PTPN(22); PTPN22; SNP; T cell; T cell antigen receptor.; TCR; antigen; autoimmunity; lymphopenia-induced proliferation; non-receptor type (22); phosphatase; protein tyrosine phosphatase; signal transduction; single nucleotide polymorphism