IFNAR and STING signaling restrict proliferation of hapten- primed CD8 T cells producing IFNγ in response to skin sensitization 2255903

Introduction Contact hypersensitivity (CHS) is a CD8 T cell-mediated response to hapten skin sensitization and challenge. While sensitization of wild-type (WT) mice induces hapten-reactive CD8 T cells that produce the effector cytokines IFNγ and IL-17 required to mediate CHS, the role of type I IFN in CHS is unclear. This study investigated a putative role for type I IFN receptor (IFNAR) signaling during hapten-specific CD8 T cell priming. Methods DNFB sensitization Results Dinitroflourobenzene (DNFB) sensitized IFNAR-/- mice had 2-3 fold more hapten-primed CD8+ T cells producing IFNγ but not IL-17, vs. WT mice in the skin draining lymph nodes and elevated frequencies of CD11ahiCD44hiCD8+ cells proliferating and expressing CXCR3 on day +5 post-sensitization. To begin to test if the IFNAR pathway is activated through cGAS binding, STING mice were sensitized. DNFB sensitized Sting-/- mice had increased numbers of hapten-primed CD8+ T cells producing IFNγ in the skin draining lymph nodes as well as higher frequencies of proliferating CD11ahiCD44hiCD8+ cells that express CXCR3. Numbers of hapten-primed CD8+ T cells producing IFNγ in the skin draining lymph nodes of sensitized Sting-/- mice remained significantly higher than WT at day +8 post sensitization despite the presence of CD4+CD25+ cells. Conclusion These results suggest IFNAR signaling via Sting is required to regulate the magnitude and duration of CHS responses through limitation of effector IFNγ producing CD8 T cell expansion.