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Single-cell analyses of patient samples and relevant mouse models have characterized many cellular subsets in RA. However, the impact of interactions between cell types is not fully understood. In this study, we temporally profiled murine arthritic synovial isolates at the single-cell level to identify perturbations similar to those found in human RA. Notably, murine macrophage subtypes like those found in RA patients were expanded in arthritis and linked to promoting the function of Th17 cells in the joint. In vitro experiments identified a capacity for murine macrophages to maintain the functionality and expansion of Th17 cells. Reciprocally, murine Th17 cell\u2013derived TNF-\u03b1 induced CD38+ macrophages that enhanced Th17 functionality. Murine synovial CD38+ macrophages were expanded during arthritis, and their depletion or blockade via TNF-\u03b1 neutralization alleviated disease while reducing IL-17A\u2013producing cells. These findings identify a cellular feedback loop that promotes Th17 cell pathogenicity through TNF-\u03b1 to drive inflammatory arthritis.<\/jats:p>","DOI":"10.4049\/jimmunol.2101025","type":"journal-article","created":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T12:50:17Z","timestamp":1645620617000},"page":"1315-1328","source":"Crossref","is-referenced-by-count":21,"title":["A Pathogenic Th17\/CD38+ Macrophage Feedback Loop Drives Inflammatory Arthritis through TNF-\u03b1"],"prefix":"10.1093","volume":"208","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8723-3389","authenticated-orcid":false,"given":"David E","family":"Muench","sequence":"first","affiliation":[{"name":"Immunology Discovery Research, Lilly Research Laboratories, Eli Lilly and Company , San Diego, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Sun","sequence":"additional","affiliation":[{"name":"Discovery Research, Lilly Research Laboratories, Eli Lilly and Company , Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anchal","family":"Sharma","sequence":"additional","affiliation":[{"name":"Research Information and Digital Solutions, Lilly Research Laboratories, Eli Lilly and Company , New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Crystal","family":"Tang","sequence":"additional","affiliation":[{"name":"Immunology Discovery Research, Lilly Research Laboratories, Eli Lilly and Company , San Diego, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7390-9683","authenticated-orcid":false,"given":"Jordan S","family":"Crampton","sequence":"additional","affiliation":[{"name":"Immunology Discovery Research, Lilly Research Laboratories, Eli Lilly and Company , San Diego, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Lao","sequence":"additional","affiliation":[{"name":"Immunology Discovery Research, Lilly Research Laboratories, Eli Lilly and Company , San Diego, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kara","family":"Kersjes","sequence":"additional","affiliation":[{"name":"Immunology Discovery Research, Lilly Research Laboratories, Eli Lilly and Company , San Diego, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8389-780X","authenticated-orcid":false,"given":"William","family":"Chang","sequence":"additional","affiliation":[{"name":"Immunology Discovery Research, Lilly Research Laboratories, Eli Lilly and Company , San Diego, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songqing","family":"Na","sequence":"additional","affiliation":[{"name":"Immunology Discovery Research, Lilly Research Laboratories, Eli Lilly and Company , San Diego, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,3,15]]},"reference":[{"key":"2025021008585047000_r1","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1056\/NEJMra1004965","article-title":"The pathogenesis of rheumatoid arthritis","volume":"365","author":"McInnes","year":"2011","journal-title":"N. 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