{"doi":"10.1111/aji.13843","title":"The role of T cell stimulated agonistic autoantibodies to the angiotensin II type I receptor (AT1‐AA) in mediating multiorgan dysfunction in IL‐17 induced hypertension during pregnancy","abstract":"PROBLEM: Preeclampsia (PE), new-onset hypertension during pregnancy accompanied by organ dysfunction, is associated with chronic inflammation including elevated IL-17, CD4+ T cells, B cells and natural killer (NK) cells. IL-17 can serve as a signal for either the adaptive or innate immune activation. We have previously shown that IL-17 contributes to increased blood pressure in association with elevated TH17 cells, NK cells and B cells secreting angiotensin II type 1 receptor agonistic autoantibodies (AT1-AA) during pregnancy. Moreover, we have shown an important role for CD4+T cells and AT1-AA in multiorgan dysfunction as measured by mitochondrial oxidative stress (mt ROS). However, we do not know the role of adaptive immune cells such as T cells or B cells secreting AT1-AA in mediating the PE phenotype in response to elevated IL-17. METHOD OF STUDY: In order to answer this question, we infused IL-17 (150 pg/day i.p.) into either Sprague Dawley (SD) or athymic nude rats via mini-osmotic pump from gestational day (GD) 14-19 of pregnancy. On GD 19, blood pressure was determined and NK cells, mtROS and respiration and AT1-AA production from B cells were measured. RESULTS: Infusion of IL-17 increased blood pressure in the presence or absence of T cells. Mean arterial pressure (MAP) increased with IL-17 from 98 ± 2 mm Hg (n = 12) to 114 ± 2 (n = 12) in SD rats and from 99 ± 4 mm Hg (n = 7) versus 115 ± 2 mm Hg (n = 7) in athymic nude rats. Similar trends were seen in NK cells and placental mt ROS. Knowing that IL-17 stimulates AT1-AA in SD pregnant rats, we included a group of SD and athymic nude pregnant rats infused with IL-17 and the AT1-AA inhibitor peptide ('n7AAc'). The inhibitor attenuated blood pressure (104.9 ± 3.2, p = .0001) and normalized NK cells and mt function in SD pregnant rats. Importantly, the AT1-AA was not produced in pregnant nude IL-17 treated rats, nor did 'n7AAc' effect MAP, in nude athymic rats. CONCLUSION: These findings suggest two conclusions; one is that IL-17 causes hypertension and multiorgan dysfunction in the absence of T cells and AT1-AA, possibly through its activation of innate cells and secondly, in the presence of T cells, blockade of the AT1-AA attenuates the effect of IL-17. This study indicates the critical effects of elevated IL-17 during pregnancy and suggest treatment modalities to consider for PE women.","journal":"American Journal of Reproductive Immunology","year":2024,"id":465280,"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":0.9635,"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":338690,"name":"Nathan Campbell","orcid":"0000-0003-0518-4219","position":1,"is_corresponding":false},{"id":337453,"name":"Evangeline Deer","orcid":"0000-0001-8004-5978","position":2,"is_corresponding":false},{"id":338691,"name":"Sarah Fitzgerald","orcid":"0000-0001-5141-560X","position":3,"is_corresponding":false},{"id":302878,"name":"Denise C. Cornelius","orcid":"0000-0002-6730-6499","position":4,"is_corresponding":false},{"id":870033,"name":"Ngoc Hoang","orcid":"0000-0003-0624-9686","position":5,"is_corresponding":false},{"id":981234,"name":"Ty Turner","orcid":"0000-0001-9660-4447","position":6,"is_corresponding":false},{"id":337454,"name":"Lorena M. Amaral","orcid":"0000-0001-7581-9182","position":7,"is_corresponding":false},{"id":1296369,"name":"James Lemon","orcid":"0000-0001-9146-6225","position":8,"is_corresponding":false},{"id":748466,"name":"Tarek Ibrahim","orcid":"0000-0003-4040-5224","position":9,"is_corresponding":false},{"id":337457,"name":"Babbette LaMarca","orcid":"0000-0002-3340-6088","position":10,"is_corresponding":false},{"id":981235,"name":"James P. Hogg","orcid":"0000-0002-2587-2070","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-19T02:04:46.201722Z","pmid":"38606700","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":[]}