{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:04:28Z","timestamp":1792785868099,"version":"4.5.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":33,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Foundation for advanced Research In Hypertension and Cardiovascular diseases","id":[{"id":"https:\/\/ror.org\/03y9tg134","id-type":"ROR","asserted-by":"crossref"}]},{"name":"MINDSHIFT"},{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The finding of autoantibodies against the angiotensin II type-1 receptor (AT1R) in human primary aldosteronism (PA) suggests a loss of immunological tolerance; however, whether autoreactive AT1R-specific T cells exist and if and how aldosterone or cortisol modulate their activity is unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Peripheral blood mononuclear cells from patients with confirmed PA and healthy donors were stimulated with overlapping AT1R peptides to identify autoreactive T cells. The chronic and rapid aldosterone effects on CD4+ and CD8+ T cells and the receptors involved were evaluated using mineralocorticoid receptor (MR) and G-protein estrogen receptor (GPER) antagonists. Cortisol effects and 11\u03b2-hydroxysteroid dehydrogenase type 2 (11\u03b2HSD2) expression were also examined. Functional cytotoxicity of AT1R-specific CD8+ clones toward human endothelial cells was assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared with healthy donors, PA patients exhibited a marked expansion of AT1R-specific CD8+ T cells recognizing the AFHYESQ epitope of the second extracellular AT1R loop, which was not detected in CD4+ cells. Both T-cell subsets expressed MR and GPER but lacked 11\u03b2HSD2 expression. Chronic aldosterone exposure enhanced CD8+ proliferation and IFN-\u03b3 production through MR. Rapid aldosterone stimulation activated CD8+ cells via MR and GPER. In CD8+ cells cortisol also increased IFN-\u03b3-production through MR. AT1R-specific CD8+ T-cell clones induced apoptosis of human endothelial cells expressing AT1R.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>PA patients harbor autoreactive AT1R-specific CD8+ T cells that respond to aldosterone and cortisol through MR and GPER. These findings identify an adaptive autoimmune mechanism in PA and provide insight into how steroid-driven T-cell activation may contribute to hypertension-mediated organ damage in aldosteronism and hypercortisolism.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ejendo\/lvag126","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T11:12:39Z","timestamp":1788520359000},"page":"443-453","source":"Crossref","is-referenced-by-count":0,"title":["Immune signatures associated with human adrenocortical hypertension"],"prefix":"10.1093","volume":"195","author":[{"given":"Riccardo","family":"Scarpa","sequence":"first","affiliation":[{"name":"Department of Medicine-DIMED University of Padova, Internal Emergency Medicine Unit, Specialized Center for Blood Pressure Disorders-Regione Veneto , Padova 35128 ,","place":["Italy"]},{"name":"Rare Diseases Referral Center, Internal Medicine I, Ca\u2019 Foncello Hospital, AULSS2 Marca Trevigiana , Treviso 31100 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