{"doi":"10.4049/immunohorizons.2300078","title":"IL-17RA–Mediated Epithelial Cell Activity Prevents Severe Inflammatory Response to <i>Helicobacter pylori</i> Infection","abstract":"Helicobacter pylori is a Gram-negative pathogen that colonizes the stomach, induces inflammation, and drives pathological changes in the stomach tissue, including gastric cancer. As the principal cytokine produced by Th17 cells, IL-17 mediates protective immunity against pathogens by inducing the activation and mobilization of neutrophils. Whereas IL-17A is largely produced by lymphocytes, the IL-17 receptor is expressed in epithelial cells, fibroblasts, and hematopoietic cells. Loss of the IL-17RA in mice results in impaired antimicrobial responses to extracellular bacteria. In the context of H. pylori infection, this is compounded by extensive inflammation in Il17ra-/- mice. In this study, Foxa3creIl17rafl/fl (Il17raΔGI-Epi) and Il17rafl/fl (control) mice were used to test the hypothesis that IL-17RA signaling, specifically in epithelial cells, protects against severe inflammation after H. pylori infection. The data indicate that Il17raΔGI-Epi mice develop increased inflammation compared with controls. Despite reduced Pigr expression, levels of IgA increased in the gastric wash, suggesting significant increase in Ag-specific activation of the T follicular helper/B cell axis. Gene expression analysis of stomach tissues indicate that both acute and chronic responses are significantly increased in Il17raΔGI-Epi mice compared with controls. These data suggest that a deficiency of IL-17RA in epithelial cells is sufficient to drive chronic inflammation and hyperactivation of the Th17/T follicular helper/B cell axis but is not required for recruitment of polymorphonuclear neutrophils. Furthermore, the data suggest that fibroblasts can produce chemokines in response to IL-17 and may contribute to H. pylori-induced inflammation through this pathway.","journal":"ImmunoHorizons","year":2024,"id":467827,"datarank":0.24141568686511508,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9563,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1127142,"name":"Matthew S. Jung","orcid":"0009-0005-1700-4870","position":1,"is_corresponding":false},{"id":1300432,"name":"Eseoghene Ogaga","orcid":"0000-0001-5754-5798","position":2,"is_corresponding":false},{"id":1219247,"name":"Nikhita Joshi","orcid":"0000-0001-9493-7926","position":3,"is_corresponding":false},{"id":864784,"name":"Lydia E. Wroblewski","orcid":"0000-0001-9205-9437","position":4,"is_corresponding":false},{"id":263090,"name":"M. Blanca Piazuelo","orcid":"0000-0002-0000-1324","position":5,"is_corresponding":false},{"id":263097,"name":"Richard M. Peek","orcid":"0000-0002-4836-5960","position":6,"is_corresponding":false},{"id":500518,"name":"Yash A. Choksi","orcid":"0000-0003-1717-4472","position":7,"is_corresponding":false},{"id":510450,"name":"Holly M. Scott Algood","orcid":"0000-0003-3735-4649","position":8,"is_corresponding":false},{"id":1091451,"name":"Lee C. Brackman","orcid":"0009-0003-2142-9658","position":0,"is_corresponding":true}],"reference_count":77,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:05:15.025255Z","pmid":"38639570","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}