Arid5a mediates an IL-17-dependent pathway that drives autoimmunity but not antifungal host defense

IL-17 contributes to the pathogenesis of certain autoimmune diseases, but conversely is essential for host defense against fungi. Antibody-based biologic drugs that neutralize IL-17 are effective in autoimmunity but can be accompanied by adverse side effects. Candida albicans is a commensal fungus that is the primary causative agent of oropharyngeal and disseminated candidiasis. Defects in IL-17 signaling cause susceptibility to candidiasis in mice and humans. A key facet of IL-17 receptor signaling involves RNA binding proteins (RBP), which orchestrate the fate of target mRNA transcripts. In tissue culture models we showed that the RBP AT-rich interacting protein 5a (Arid5a) promotes the stability and/or translation of multiple IL-17-dependent mRNAs. Moreover, during OPC, Arid5a is elevated within the oral mucosa in an IL-17-dependent manner. However, the contribution of Arid5a to IL-17-driven events in vivo is poorly defined. Here, we used CRISPR/Cas9 to generate mice lacking Arid5a. Arid5a-/- mice were fully resistant to experimental autoimmune encephalomyelitis (EAE), an autoimmune setting in which IL-17 signaling drives pathology. Surprisingly, Arid5a-/- mice were resistant to OPC and systemic candidiasis, similar to immunocompetent WT mice and contrasting with mice defective in IL-17 signaling. Therefore, Arid5a-dependent signals mediate pathology in autoimmunity yet are not required for immunity to candidiasis, indicating that selective targeting of IL-17 signaling pathway components may be a viable strategy for development of therapeutics that spare IL-17-driven host defense.