title: The role of PTPN22 risk variant in the development of autoimmunity: finding common ground between mouse and human.
abstract: The PTPN22 1858T variant was among the first single nucleotide polymorphisms to be associated with multiple autoimmune diseases. Lymphocyte tyrosine phosphatase, a coding variant within the tyrosine phosphatases, is known to participate in AgR signaling; the impact of this variant on the immune response and its role in the development of autoimmunity have been a focus of study. These studies used a series of approaches, including transfected cell lines, animal models, and primary human lymphocytes, and identified multiple alterations in cell signaling and function linked to the PTPN22 variant. Conflicting findings led to questions of how best to study the role of this variant in human autoimmunity. In this review, we discuss these differences and the factors that may account for them, as well as show how an integrated approach can lead to a more complete understanding of the mechanisms that promote autoimmunity in the context of the PTPN22 1858T risk variant.
authors: Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 98195; Department of Immunology, University of Washington School of Medicine, Seattle, WA 98195; Seattle Children's Research Institute, Seattle, WA 98101; and jbuckner@benaroyaresearch.org drawling@u.washington.edu.
authors: David J
authors: DJ
authors: Rawlings
authors: Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 98195; Seattle Children's Research Institute, Seattle, WA 98101; and.
authors: Xuezhi
authors: X
authors: Dai
authors: Translational Research Program, Benaroya Research Institute, Seattle, WA 98101 jbuckner@benaroyaresearch.org drawling@u.washington.edu.
authors: Jane H
authors: JH
authors: Buckner
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics*; D004195:Disease Models, Animal; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D051379:Mice; D020641:Polymorphism, Single Nucleotide; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics*; D012306:Risk
chemical_list: D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22