768 Type I interferons modulate ultraviolet radiation induced suppression of immune responses via Stimulator of Interferon Genes (STING)

Abstract

UV (ultraviolet) B induced immune suppression contributes in a major way to the growth and development of UVB-induced skin cancers. Type I interferons (IFNs) are cytokines that play a role in regulation of proliferation, differentiation, and immune function. All characterized type I IFNs transmit their signals through the type I IFN receptor (IFNAR) composed of IFNAR1 and IFNAR2 components. Loss of either subunit results in complete abrogation of receptor function. There is limited information on the role for type I IFNs (IFN-α/β) signaling in UVB induced immune responses. Stimulator of IFN genes (STING) is an adaptor that responds to intracytoplasmic DNA by stimulating the production of type I IFN. The purpose of this study was to determine whether type I IFNs contributed to UV-induced DNA damage and immunosuppression via Stimulator of Interferon genes (STING) pathway. IFNAR1 deficient (IFNAR1-/-) and STING deficient (STING-/-) on C57BL/6 background and wild type (WT) mice were subjected to a local UVB regimen consisting of 100 mJ/cm2 UVB radiation for 4 days followed by sensitization with the hapten 2, 4-dinitrofluorobenzene (DNFB). UVB radiation in wild type mice induced significant (p<0.001) suppression of contact hypersensitivity response which was greatly enhanced (p<0.001) in IFNAR1-/- and STING-/- mice. The enhanced immune suppression was associated with significant decrease (p<0.001) in CD8+ T-cells and increase (p<0.001) in CD4+CD25+Foxp3+ populations in IFNAR1-/- and STING-/- mice when compared with WT mice. These findings can be used to develop type I IFN agonists for prevention against UVB induced immune suppression.