Dendritic cell intrinsic role of <i>Ptpn22</i>and its pro-autoimmune allele enhance anti-viral immunity

Abstract The tyrosine phosphatase PTPN22 encodes the enzyme Lyp (PEP in mice) all immune cells. 5–10% of North American population expresses autoimmunity risk allele 1858C&amp;gt;T (rs2476601) causing amino acid substitution R620W (R619W mice). This mutation alters lymphocyte activation, toll-like receptor signaling, and cytokine production. Ptpn22 knockout (PEP-null) alternative allele-expressing (PEP-R619W) mice clear persistent virus LCMV-cl13, have enhanced anti-viral T cell function, a more immunostimulatory dendritic (DC) phenotype compared to wildtype (PEP-WT). Adoptive transfer studies suggest extrinsic mechanism driving function PEP-null -R619W animals. However, relative contribution PEP-differing non-T cells during infection is not known. We hypothesize that DC, as sole cell, critical increased immunity.To interrogate this, we employ CD11c conditional knock out (cKO) bone marrow derived DC (BMDC) cultures from PEP-WT, -null, mice. During LCMV-cl13 infection, cKO improved disease outcome WT In cell: co-culture assay, both PEP-R619W DCs lead CD4 over DCs. Also, BMDCs changed response infection. Taken together, these data its intrinsic mechanisms alter immunity. Results this study complete understanding cellular molecular mechanisms, particularly common Supported by grants University Kansas (KU), KU CBID CoBRE Research Award, Center for Genomics.