{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T16:08:57Z","timestamp":1789834137411,"version":"4.0.1"},"reference-count":80,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2024,1,5]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>T cells are central to the immune responses contributing to hypertension. LGMN (legumain) is highly expressed in T cells; however, its role in the pathogenesis of hypertension remains unclear.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>\n              Peripheral blood samples were collected from patients with hypertension, and cluster of differentiation (CD)4+ T cells were sorted for gene expression and Western blotting analysis. TLGMNKO (T cell\u2013specific LGMN-knockout) mice (Lgmn\n              <jats:sup>f\/f<\/jats:sup>\n              \/CD4\n              <jats:sup>Cre<\/jats:sup>\n              ), regulatory T cell (Treg)\u2013specific LGMN-knockout mice (Lgmn\n              <jats:sup>f\/f<\/jats:sup>\n              \/Foxp3\n              <jats:sup>YFP Cre<\/jats:sup>\n              ), and RR-11a (LGMN inhibitor)\u2013treated C57BL\/6 mice were infused with Ang II (angiotensin II) or deoxycorticosterone acetate\/salt to establish hypertensive animal models. Flow cytometry, 4-dimensional label-free proteomics, coimmunoprecipitation, Treg suppression, and in vivo Treg depletion or adoptive transfer were used to delineate the functional importance of T-cell LGMN in hypertension development.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>LGMN mRNA expression was increased in CD4+ T cells isolated from hypertensive patients and mice, was positively correlated with both systolic and diastolic blood pressure, and was negatively correlated with serum IL (interleukin)-10 levels. TLGMNKO mice exhibited reduced Ang II\u2013induced or deoxycorticosterone acetate\/salt\u2013induced hypertension and target organ damage relative to wild-type (WT) mice. Genetic and pharmacological inhibition of LGMN blocked Ang II\u2013induced or deoxycorticosterone acetate\/salt\u2013induced immunoinhibitory Treg reduction in the kidneys and blood. Anti-CD25 antibody depletion of Tregs abolished the protective effects against Ang II\u2013induced hypertension in TLGMNKO mice, and LGMN deletion in Tregs prevented Ang II\u2013induced hypertension in mice. Mechanistically, endogenous LGMN impaired Treg differentiation and function by directly interacting with and facilitating the degradation of TRAF6 (tumor necrosis factor receptor\u2013associated factor 6) via chaperone-mediated autophagy, thereby inhibiting NF-\u03baB (nuclear factor kappa B) activation. Adoptive transfer of LGMN-deficient Tregs reversed Ang II\u2013induced hypertension, whereas depletion of TRAF6 in LGMN-deficient Tregs blocked the protective effects.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>LGMN deficiency in T cells prevents hypertension and its complications by promoting Treg differentiation and function. Specifically targeting LGMN in Tregs may be an innovative approach for hypertension treatment.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.123.322835","type":"journal-article","created":{"date-parts":[[2023,12,4]],"date-time":"2023-12-04T05:00:15Z","timestamp":1701666015000},"page":"9-29","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":27,"title":["CD4+ T-Cell Legumain Deficiency Attenuates Hypertensive Damage via Preservation of TRAF6"],"prefix":"10.1161","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4814-1369","authenticated-orcid":true,"given":"Yuhu","family":"He","sequence":"first","affiliation":[{"name":"Departments of Cardiology (Y.H., P.Z., X.Z., J. 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