{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Dixon BREA"],"funding":["BLRD VA","NIDDK NIH HHS","NCI NIH HHS"],"pagination":["116-129"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9364271"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["6(2)"],"pubmed_abstract":["IL-17R signaling is required for control of extracellular pathogens and is also implicated in development of chronic inflammatory processes. The response to the human pathogen <i>Helicobacter pylori</i> 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 <i>H. pylori</i> colonization in the gastric mucosa. Unexpectedly, <i>H. pylori</i>-infected <i>Il17ra</i> <sup>-/-</sup> mice had significantly more chronic inflammation than <i>H. pylori</i>-infected 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 <i>H. pylori</i> 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 <i>H. pylori</i>, 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 <i>Il17ra</i> <sup>-/-</sup> mice was not attributed to a T cell-intrinsic defect. These data imply that IL-17A and IL-17F may have overlapping roles in maintenance of the gastric mucosal response to infection."],"journal":["ImmunoHorizons"],"pubmed_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."],"pmcid":["PMC9364271"],"funding_grant_id":["I01 BX000915","P30 CA068485","U24 DK059637","P30 DK058404"],"pubmed_authors":["Dixon BREA","Li J","Lee TJ","Goettel JA","Contreras Healey DC","Algood HMS","Piazuelo MB"],"additional_accession":[]},"is_claimable":false,"name":"IL-17 Receptor Signaling through IL-17A or IL-17F Is Sufficient to Maintain Innate Response and Control of <i>Helicobacter pylori</i> Immunopathogenesis.","description":"IL-17R signaling is required for control of extracellular pathogens and is also implicated in development of chronic inflammatory processes. The response to the human pathogen <i>Helicobacter pylori</i> 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 <i>H. pylori</i> colonization in the gastric mucosa. Unexpectedly, <i>H. pylori</i>-infected <i>Il17ra</i> <sup>-/-</sup> mice had significantly more chronic inflammation than <i>H. pylori</i>-infected 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 <i>H. pylori</i> 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 <i>H. pylori</i>, 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 <i>Il17ra</i> <sup>-/-</sup> mice was not attributed to a T cell-intrinsic defect. These data imply that IL-17A and IL-17F may have overlapping roles in maintenance of the gastric mucosal response to infection.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Feb","modification":"2024-11-14T18:17:38.753Z","creation":"2024-11-14T18:17:38.753Z"},"accession":"S-EPMC9364271","cross_references":{"pubmed":["35144998"],"doi":["10.4049/immunohorizons.2000072"]}}