title: The effect of the autoimmunity-associated gene, PTPN22, on a BXSB-derived model of lupus.
abstract: A single nucleotide polymorphism in PTPN22 is linked to increased disease susceptibility in a range of autoimmune diseases including systemic lupus erythematosus (SLE). PTPN22 encodes the Lyp phosphatase that dampens TCR signaling and is necessary for signaling downstream of toll-like receptors in myeloid cells. To understand these dual functions in disease, we examined the impact of deficiency in PTPN22 on a spontaneous murine model of SLE. Male PTPN22 KO mice carrying BXSB chromosome 1 and the Yaa disease accelerating factor developed disease at a similar rate and severity as PTPN22 WT. In contrast, although female mice showed no differences in survival in the absence of PTPN22, autoantibody production was significantly increased and splenic populations associated with pathogenesis in this model were expanded in the PTPN22 KO group. These findings support the notion that when coupled with other predisposing autoimmunity genes, PTPN22 deficiency contributes to a predisposition to lupus pathogenesis.
authors.affiliation: Department of Immunity and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Maine
authors.affiliation: Department of Immunity and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Kristi
authors.initials: K
authors.lastname: Marquardt
authors.affiliation: Department of Immunity and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Scatizzi
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: K Michael
authors.initials: KM
authors.lastname: Pollard
authors.affiliation: Department of Immunity and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Dwight H
authors.initials: DH
authors.lastname: Kono
authors.affiliation: Department of Immunity and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: lsherman@scripps.edu.
authors.forename: Linda A
authors.initials: LA
authors.lastname: Sherman
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics* / Q000378:metabolism*
chemical_list: C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22
keywords: Autoantibodies; BXSB; PTPN22; Systemic lupus erythematosus; T follicular helper cells; Tolerance