{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:46:20Z","timestamp":1790253980741,"version":"4.1.0"},"reference-count":55,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,3,3]],"date-time":"2020-03-03T00:00:00Z","timestamp":1583193600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST106-2511-S-010 -001 -MY3"],"award-info":[{"award-number":["MOST106-2511-S-010 -001 -MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Bacterial translocation (BT) and splenomegaly contribute to cirrhosis-associated immune dysfunction (CAID) including T cell depletion, infection, and chronic inflammation. \u03b2-blockers have been reported to decrease BT and improve splenomegaly. This study explores the modulation of \u03b21 and \u03b22 adrenergic receptors (ADRB1\/ADRB2) by propranolol treatment on the peripheral and splenic immune dysfunction of cirrhotic mice. In vivo experiments were performed in bile duct ligation (BDL)- and thioacetamide (TAA)-cirrhotic mice receiving two weeks of propranolol treatment. Acute effects of propranolol were evaluated in T-helper (Th) cells isolated from spleen of cirrhotic mice. Over-expression of \u03b21 and \u03b22 adrenergic receptors (ADRB1\/ADRB2) in spleen and T lymphocytes was associated with high peripheral\/splenic lipopolysaccharide binding protein levels. Moreover, a decrease in Th cells percentage, increase in Treg subset, and cytokines were accompanied by increased apoptosis, proliferation, and reduced white pulp hyperplasia in cirrhotic mice, which were counteracted by propranolol treatment. The Th-cell depletion, systemic inflammation, BT, and infection were improved by chronic propranolol treatment. Acute propranolol treatment inhibited apoptosis, Treg-conditioned differentiation, and promoted Th2-conditioned differentiation through ADRB-cyclic adenosine monophosphate (cAMP) signals in cirrhotic mice. In conclusion, suppression of ADRB1 and ADRB2 expressions in spleen and splenic T lymphocytes by acute and chronic propranolol treatment ameliorate systemic and splenic immune dysfunction in cirrhosis.<\/jats:p>","DOI":"10.3390\/cells9030604","type":"journal-article","created":{"date-parts":[[2020,3,3]],"date-time":"2020-03-03T13:06:23Z","timestamp":1583240783000},"page":"604","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Propranolol Suppresses the T-Helper Cell Depletion-Related Immune Dysfunction in Cirrhotic Mice"],"prefix":"10.3390","volume":"9","author":[{"given":"Hung-Cheng","family":"Tsai","sequence":"first","affiliation":[{"name":"Division of Allergy and Immunology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"Faculty of Medicine, School of Medicine, National Yang-Ming University School of Medicine, Taipei 11217, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-Fu","family":"Hsu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, School of Medicine, National Yang-Ming University School of Medicine, Taipei 11217, Taiwan"},{"name":"Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1313-4628","authenticated-orcid":false,"given":"Chia-Chang","family":"Huang","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, School of Medicine, National Yang-Ming University School of Medicine, Taipei 11217, Taiwan"},{"name":"Division of Clinical Skills Center, Department of medical education, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei 11217, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiang-Fen","family":"Huang","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, School of Medicine, National Yang-Ming University School of Medicine, Taipei 11217, Taiwan"},{"name":"Division of Infection, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzu-Hao","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"Faculty of Medicine, School of Medicine, National Yang-Ming University School of Medicine, Taipei 11217, Taiwan"},{"name":"Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei 11217, Taiwan"},{"name":"Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Foundation, 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Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han-Chieh","family":"Lin","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, School of Medicine, National Yang-Ming University School of Medicine, Taipei 11217, Taiwan"},{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/S0140-6736(74)92015-7","article-title":"Reduction in circulating T lymphocytes in alcoholic liver disease","volume":"7879","author":"Bernstein","year":"1974","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"G269","DOI":"10.1152\/ajpgi.00200.2014","article-title":"Cytotoxic T lymphocytes and natural killer cells display impaired cytotoxic functions and reduced 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