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Ab-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, which orchestrate the fate of target mRNA transcripts. In tissue culture models we showed that the RNA-binding protein AT-rich interaction domain 5A (Arid5a) promotes the stability and\/or translation of multiple IL-17\u2013dependent mRNAs. Moreover, during oropharyngeal candidiasis, Arid5a is elevated within the oral mucosa in an IL-17\u2013dependent manner. However, the contribution of Arid5a to IL-17\u2013driven events in vivo is poorly defined. In this study, we used CRISPR-Cas9 to generate mice lacking Arid5a. Arid5a\u2212\/\u2212 mice were fully resistant to experimental autoimmune encephalomyelitis, an autoimmune setting in which IL-17 signaling drives pathology. Surprisingly, Arid5a\u2212\/\u2212 mice were resistant to oropharyngeal candidiasis and systemic candidiasis, similar to immunocompetent wild-type mice and contrasting with mice defective in IL-17 signaling. Therefore, Arid5a-dependent signals mediate pathology in autoimmunity and 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\u2013driven host defense.<\/jats:p>","DOI":"10.4049\/jimmunol.2200132","type":"journal-article","created":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T01:13:55Z","timestamp":1672708435000},"page":"1138-1145","source":"Crossref","is-referenced-by-count":11,"title":["Arid5a Mediates an IL-17\u2013Dependent Pathway That Drives Autoimmunity but Not Antifungal Host Defense"],"prefix":"10.1093","volume":"209","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4971-3728","authenticated-orcid":false,"given":"Tiffany C","family":"Taylor","sequence":"first","affiliation":[{"name":"Division of Rheumatology & Clinical Immunology, University of Pittsburgh , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6743-4004","authenticated-orcid":false,"given":"Yang","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Rheumatology & Clinical Immunology, University of Pittsburgh , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9474-390X","authenticated-orcid":false,"given":"De-Dong","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Rheumatology & Clinical Immunology, University of Pittsburgh , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6591-9515","authenticated-orcid":false,"given":"Saikat","family":"Majumder","sequence":"additional","affiliation":[{"name":"Division of Rheumatology & Clinical Immunology, University of Pittsburgh , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mandy J","family":"McGeachy","sequence":"additional","affiliation":[{"name":"Division of Rheumatology & Clinical Immunology, University of Pittsburgh , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Partha S","family":"Biswas","sequence":"additional","affiliation":[{"name":"Division of Rheumatology & Clinical Immunology, University of Pittsburgh , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2607-8642","authenticated-orcid":false,"given":"Sebastien","family":"Gingras","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Pittsburgh , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8511-2041","authenticated-orcid":false,"given":"Sarah L","family":"Gaffen","sequence":"additional","affiliation":[{"name":"Division of Rheumatology & Clinical Immunology, University of Pittsburgh , Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,9,15]]},"reference":[{"key":"2025021008301303100_r1","doi-asserted-by":"crossref","first-page":"780","DOI":"10.4049\/jimmunol.1500909","article-title":"IL-17-mediated immunity to the opportunistic fungal pathogen Candida albicans","volume":"195","author":"Conti","year":"2015","journal-title":"J. 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