Ets1 and IL17RA cooperate to regulate autoimmune responses as well as skin immunity to Staphylococcus aureus
Autoimmune diseases display many changes to the immune environment. The lineage-specific transcription factor Ets1 has been associated with autoimmune diseases including SLE. Ets1KO mice develop significant autoimmune disease with an expansion of IL-17 expressing lymphocytes. To ascertain the role of IL-17 in the phenotype of Ets1KO mice, mice lacking both Ets1 and IL17Ra were generated. These double-knockout mice (DKO) were found to develop significant autoimmune disease characterized by development of spontaneous skin lesions. To ascertain the potential causative factors contributing to the lesional skin development, RNA sequencing was conducted on ventral neck skin bulk RNA samples harvested from wild-type, Ets1KO, IL17RaKO, and DKO animals. We report here that Ets1 and IL17Ra deletion results in significant gene expression changes. Among the changes in gene expression reported here is significantly elevated expression of proinflammatory cytokines commonly part of the normal skin immune response to wounding and/or infection. Together these data suggest that Ets1 and Il17Ra signaling interact resulting in significantly altered immune related gene expression in the skin of DKO mice. Overall design: Ventral neck skin harvested from DKO, single-kncout controls, and wild type mice. Extracted RNA was subjected to bulk RNA sequencing to ascertain differentially expressed genes as a result of Ets1 and/or IL17Ra deletion in comparison to WT skin.