{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T11:13:42Z","timestamp":1793186022724,"version":"4.5.0"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"18","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2020,11,3]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>\n              Hydrogen sulfide (H\n              <jats:sub>2<\/jats:sub>\n              S) has antihypertension and anti-inflammatory effects, and its endogenous-generation key enzyme cystathionine \u03b3 lyase (CSE) is expressed in CD4\n              <jats:sup>+<\/jats:sup>\n              T cells. However, the role of CD4\n              <jats:sup>+<\/jats:sup>\n              T-cell endogenous CSE\/H\n              <jats:sub>2<\/jats:sub>\n              S in the development of hypertension is unclear.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>\n              Peripheral blood lymphocytes were isolated from hypertensive patients or spontaneously hypertensive rats, then H\n              <jats:sub>2<\/jats:sub>\n              S production and expression of its generation enzymes, cystathionine \u03b2 synthase and CSE, were measured to determine the major H\n              <jats:sub>2<\/jats:sub>\n              S generation system changes in hypertension. Mice with CSE-specific knockout in T cells (conditional knockout, by CD4\n              <jats:sup>cre<\/jats:sup>\n              mice hybridization) and CD4 null mice were generated for investigating the pathophysiological relevance of the CSE\/H\n              <jats:sub>2<\/jats:sub>\n              S system.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              In lymphocytes, H\n              <jats:sub>2<\/jats:sub>\n              S from CSE, but not cystathionine \u03b2 synthase, responded to blood pressure changes, supported by lymphocyte CSE protein changes and a negative correlation between H\n              <jats:sub>2<\/jats:sub>\n              S production with systolic blood pressure and diastolic blood pressure, but positive correlation with the serum level of interleukin 10 (an anti-inflammatory cytokine). Deletion of CSE in T cells elevated BP (5\u20138 mm Hg) under the physiological condition and exacerbated angiotensin II\u2013induced hypertension. In keeping with hypertension, mesenteric artery dilation impaired association with arterial inflammation, an effect attributed to reduced immunoinhibitory T regulatory cell (Treg) numbers in the blood and kidney, thus causing excess CD4\n              <jats:sup>+<\/jats:sup>\n              and CD8\n              <jats:sup>+<\/jats:sup>\n              T cell infiltration in perivascular adipose tissues and kidney. CSE knockout CD4\n              <jats:sup>+<\/jats:sup>\n              T cell transfer into CD4 null mice, also showed the similar phenotypes\u2019 confirming the role of endogenous CSE\/H\n              <jats:sub>2<\/jats:sub>\n              S action. Adoptive transfer of Tregs (to conditional knockout mice) reversed hypertension, vascular relaxation impairment, and immunocyte infiltration, which confirmed that conditional knockout\u2013induced hypertension was attributable, in part, to the reduced Treg numbers. Mechanistically, endogenous CSE\/H\n              <jats:sub>2<\/jats:sub>\n              S promoted Treg differentiation and proliferation by activating AMP-activated protein kinase. In part, it depended on activation of its upstream kinase, liver kinase B1, by sulfhydration to facilitate its substrate binding and phosphorylation.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion:<\/jats:title>\n            <jats:p>\n              The constitutive sulfhydration of liver kinase B1 by CSE-derived H\n              <jats:sub>2<\/jats:sub>\n              S activates its target kinase, AMP-activated protein kinase, and promotes Treg differentiation and proliferation, which attenuates the vascular and renal immune-inflammation, thereby preventing hypertension.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.119.045344","type":"journal-article","created":{"date-parts":[[2020,9,9]],"date-time":"2020-09-09T09:03:18Z","timestamp":1599642198000},"page":"1752-1769","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":74,"title":["CD4\n            <sup>+<\/sup>\n            T-Cell Endogenous Cystathionine \u03b3 Lyase\u2013Hydrogen Sulfide Attenuates Hypertension by Sulfhydrating Liver Kinase B1 to Promote T Regulatory Cell Differentiation and Proliferation"],"prefix":"10.1161","volume":"142","author":[{"given":"Changting","family":"Cui","sequence":"first","affiliation":[{"name":"Hypertension Center, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Beijing, P.R. China (C.C., Z.C., W.W., S.y.L., Jun Cai, B.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinghui","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic Medical Science; Peking University Health Science Center, Beijing, P.R. China (J.F., Q.C., J.Y., C.T., G.X.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Zeng","sequence":"additional","affiliation":[{"name":"Health Management Institute, the Second Medical Center &amp; National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, P.R. China (Q.Z., Y.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyan","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongda Hospital Affiliated to Southeast University, Nanjing, Jiangsu. P.R. China (Junyan Cai)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongzeng","family":"Chen","sequence":"additional","affiliation":[{"name":"Health Management Institute, the Second Medical Center &amp; National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, P.R. China (Q.Z., Y.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenzhen","family":"Chen","sequence":"additional","affiliation":[{"name":"Hypertension Center, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Beijing, P.R. China (C.C., Z.C., W.W., S.y.L., Jun Cai, B.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjie","family":"Wang","sequence":"additional","affiliation":[{"name":"Hypertension Center, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Beijing, P.R. China (C.C., Z.C., W.W., S.y.L., Jun Cai, B.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang yue","family":"Li","sequence":"additional","affiliation":[{"name":"Hypertension Center, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Beijing, P.R. China (C.C., Z.C., W.W., S.y.L., Jun Cai, B.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3018-5221","authenticated-orcid":true,"given":"Qinghua","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic Medical Science; Peking University Health Science Center, Beijing, P.R. China (J.F., Q.C., J.Y., C.T., G.X.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8150-2923","authenticated-orcid":true,"given":"Jichun","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic Medical Science; Peking University Health Science Center, Beijing, P.R. 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