The minor allele of Ptpn22 changes pro-inflammatory cytokine production in dendritic cells 4699

Abstract Description Dendritic cells (DCs) produce cytokines with direct antiviral properties, such as type I interferon (IFN-I), as well as polarizing cytokines that promote T cell differentiation (e.g. IL-12). Previously, we found that the common minor allele of the immunoregulatory gene Ptpn22 (PEP-R619W) promotes antiviral immunity in DCs and T cells. However, the mechanisms by which Ptpn22, and its minor allele, influence antiviral immune function remain largely unknown. Prior studies report that mice without Ptpn22 expression (PEP-null) have reduced IFN-I production in DCs following LPS exposure. However, they did not investigate the impact of PEP-R619W on IFN-I production during virus infection. We hypothesize that mice expressing PEP-R619W possess an immunostimulatory cytokine profile which enhances viral clearance. To test this, we measured the production of IFNβ, and other pro-inflammatory cytokines including IL-2, IL-12, and TNF-α, following exposure to LPS, 3p-hpRNA (RIG-I agonist), or virus. Contrary to previous studies, our results show Ptpn22, and its minor allele do not impact IFNβ production. However, PEP-R619W DCs produce more IL-2 and less TNF-α compared to wildtype DCs. This study demonstrates that PEP-R619W alters the production of various pro-inflammatory cytokines which may promote viral clearance. These results provide further insight into the mechanisms in which the minor allele of Ptpn22 enhances the anti-viral immune response. Funding Sources Supported by the Kansas INBRE, P20 GM103418 Topic Categories Cytokines and Chemokines and Their Receptors (CCR)