{"doi":"10.1093/function/zqaf001","title":"Aryl Hydrocarbon Receptor Activation Promotes Effector CD4+ T Cell Homeostasis and Restrains Salt-Sensitive Hypertension","abstract":"Excess dietary salt and salt-sensitivity contribute to cardiovascular disease. Distinct T cell phenotypic responses to high salt and hypertension, as well as influences from environmental cues, are not well understood. The aryl hydrocarbon receptor (AhR) is activated by dietary ligands, promoting T cell and systemic homeostasis. We hypothesized that activating AhR supports CD4+ homeostatic functions, such as cytokine production and mobilization, in response to high salt intake while mitigating salt-sensitive hypertension. In the intestinal mucosa, we demonstrate that a high-salt diet (HSD) is a key driving factor, independent of hypertension, in diminishing interleukin 17A (IL-17A) production by CD4+ T (Th17) cells without disrupting circulating cytokines associated with Th17 function. Previous studies suggest that hypertensive patients and individuals on a HSD are deficient in AhR ligands or agonistic metabolites. We found that activating AhR augments Th17 cells during experimental salt-sensitive hypertension. Further, we demonstrate that activating AhR in vitro contributes to sustaining Th17 cells in the setting of excess salt. Using photoconvertible Kikume Green-Red mice, we also revealed that HSD drives CD4+ T cell mobilization. Next, we found that excess salt augments T cell mobilization markers, validating HSD-driven T cell migration. Also, we found that activating AhR mitigates HSD-induced T cell migration markers. Using telemetry in a model of experimental salt-sensitivity, we found that activating AhR prevents the development of salt-sensitive hypertension. Collectively, stimulating AhR through dietary ligands facilitates immunologic and systemic functions amid excess salt intake and restrains the development of salt-sensitive hypertension.","journal":"Function","year":2025,"id":537825,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"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":0.9545,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":303565,"name":"Claudia Edell","orcid":null,"position":1,"is_corresponding":false},{"id":1181006,"name":"Luke S. Dunaway","orcid":"0000-0002-7458-9669","position":2,"is_corresponding":false},{"id":978362,"name":"Cailin Kellum","orcid":"0000-0003-0113-6711","position":3,"is_corresponding":false},{"id":1111505,"name":"Rachel Q Muir","orcid":"0000-0002-7671-0776","position":4,"is_corresponding":false},{"id":442241,"name":"Melissa Jennings","orcid":"0000-0002-6814-8525","position":5,"is_corresponding":false},{"id":771037,"name":"Jackson Colson","orcid":null,"position":6,"is_corresponding":false},{"id":485176,"name":"Carmen De Miguel","orcid":"0000-0002-2323-3670","position":7,"is_corresponding":false},{"id":1001805,"name":"Megan K Rhoads","orcid":"0000-0001-7494-9815","position":8,"is_corresponding":false},{"id":1112345,"name":"Ashlyn A. Buzzelli","orcid":"0000-0002-1704-3619","position":9,"is_corresponding":false},{"id":253539,"name":"Laurie E. Harrington","orcid":"0000-0002-6832-9529","position":10,"is_corresponding":false},{"id":273533,"name":"Selene Meza‐Perez","orcid":"0000-0001-7881-6964","position":11,"is_corresponding":false},{"id":273532,"name":"Troy D. Randall","orcid":"0000-0003-0643-0311","position":12,"is_corresponding":false},{"id":442364,"name":"Davide Botta","orcid":"0000-0003-3926-0662","position":13,"is_corresponding":false},{"id":462024,"name":"Dominik N. Müller","orcid":"0000-0003-3650-5644","position":14,"is_corresponding":false},{"id":414211,"name":"David M. Pollock","orcid":"0000-0002-0233-2362","position":15,"is_corresponding":false},{"id":107275,"name":"Craig L. Maynard","orcid":"0000-0001-5876-8168","position":16,"is_corresponding":false},{"id":687591,"name":"Jennifer S. Pollock","orcid":"0000-0003-1956-0449","position":17,"is_corresponding":false},{"id":827093,"name":"Patrick A. 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