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The response to the human pathogen Helicobacter pylori results in Th1 and Th17 cell activation and a chronic inflammatory process that can lead to adverse outcomes, such as gastric cancer. Previously, we identified IL-17RA as a requirement for the recruitment of neutrophils and control of H. pylori colonization in the gastric mucosa. Unexpectedly, H. pylori\u2013infected Il17ra\u2212\/\u2212 mice had significantly more chronic inflammation than H. pylori\u2013infected wild-type mice. In this study, human epithelial cell lines and murine models were used to investigate differential roles for IL-17A, IL-17F, and IL-17A\/F during H. pylori infection. Moreover, the hypothesis that IL-17RA signaling, specifically in lymphocytes, provides an autocrine feedback loop that downregulates Th17 cytokine production was investigated. The data indicate that epithelial cells exhibit a stronger response to IL-17A and IL-17A\/F than IL-17F, and that IL-17A and IL-17A\/F can synergize with TNF and IL-22 to induce antimicrobial genes of gastric epithelial cells. In vivo deficiencies of IL-17A or IL-17F alone did not significantly change the immunopathological response to H. pylori, but if both cytokines were absent, a hyperinflammatory lymphocytic response developed. Using a cre\/flox targeting approach for IL-17RA combined with infection, our findings demonstrate that increased chronic inflammation in Il17ra\u2212\/\u2212 mice was not attributed to a T cell\u2013intrinsic defect. These data imply that IL-17A and IL-17F may have overlapping roles in maintenance of the gastric mucosal response to infection.<\/jats:p>","DOI":"10.4049\/immunohorizons.2000072","type":"journal-article","created":{"date-parts":[[2022,2,10]],"date-time":"2022-02-10T15:05:16Z","timestamp":1644505516000},"page":"116-129","source":"Crossref","is-referenced-by-count":12,"title":["IL-17 Receptor Signaling through IL-17A or IL-17F Is Sufficient to Maintain Innate Response and Control of <i>Helicobacter pylori<\/i> Immunopathogenesis"],"prefix":"10.1093","volume":"6","author":[{"given":"Beverly R E A","family":"Dixon","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Infectious Disease, Vanderbilt University School of Medicine, Vanderbilt University Medical Center , Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany J","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Disease, Vanderbilt University School of Medicine, Vanderbilt University Medical Center , Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana C","family":"Contreras Healey","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Vanderbilt University Medical Center , Nashville, TN"},{"name":"Vanderbilt Institute of Infection, Immunity, and Inflammation, Vanderbilt University Medical Center , Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Vanderbilt University Medical Center , Nashville, TN"},{"name":"Vanderbilt Institute of Infection, Immunity, and Inflammation, Vanderbilt University Medical Center , Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0749-2357","authenticated-orcid":false,"given":"Jeremy A","family":"Goettel","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Vanderbilt University Medical Center , Nashville, TN"},{"name":"Vanderbilt Institute of Infection, Immunity, and Inflammation, Vanderbilt University Medical Center , Nashville, TN"},{"name":"Department of Medicine, Division of Gastroenterology, Vanderbilt University School of Medicine, Vanderbilt University Medical Center , Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M Blanca","family":"Piazuelo","sequence":"additional","affiliation":[{"name":"Vanderbilt Institute of Infection, Immunity, and Inflammation, Vanderbilt University Medical Center , Nashville, TN"},{"name":"Department of Medicine, Division of Gastroenterology, Vanderbilt University School of Medicine, Vanderbilt University Medical Center , Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3735-4649","authenticated-orcid":false,"given":"Holly M Scott","family":"Algood","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Disease, Vanderbilt University School of Medicine, Vanderbilt University Medical Center , Nashville, TN"},{"name":"Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Vanderbilt University Medical Center , Nashville, TN"},{"name":"Vanderbilt Institute of Infection, Immunity, and Inflammation, Vanderbilt University Medical Center , Nashville, TN"},{"name":"Tennessee Valley Healthcare System, Department of Veterans Affairs , Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,2,1]]},"reference":[{"key":"2025010703511208000_r1","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/nature04870","article-title":"Nuclear factor-kappaB in cancer development and progression","volume":"441","author":"Karin","year":"2006","journal-title":"Nature"},{"key":"2025010703511208000_r2","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1158\/1078-0432.CCR-08-0149","article-title":"Targeting inflammatory pathways for prevention and therapy of cancer: short-term friend, long-term foe","volume":"15","author":"Aggarwal","year":"2009","journal-title":"Clin. 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