{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T04:14:12Z","timestamp":1773893652070,"version":"3.50.1"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82170009"],"award-info":[{"award-number":["82170009"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81873958"],"award-info":[{"award-number":["81873958"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82001684"],"award-info":[{"award-number":["82001684"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the National Key Research and Development Plan","award":["2020YFA0907200"],"award-info":[{"award-number":["2020YFA0907200"]}]},{"name":"the Guangdong Scientific and Technological Foundation","award":["2019B1515120041"],"award-info":[{"award-number":["2019B1515120041"]}]},{"name":"the Guangdong Scientific and Technological Foundation","award":["2020B1111170014"],"award-info":[{"award-number":["2020B1111170014"]}]},{"name":"the Guangdong Scientific and Technologic Foundation","award":["2019A1515110055"],"award-info":[{"award-number":["2019A1515110055"]}]},{"name":"the Shenzhen Scientific and Technologic Foundation","award":["KCXFZ202002011007083"],"award-info":[{"award-number":["KCXFZ202002011007083"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The cannabinoid receptor 2 (CB2) is a receptor mainly expressed in immune cells and believed to be immunosuppressive in infective or inflammatory models. However, its role in sepsis has not been fully elucidated. In this study, we delineate the function and mechanism of CB2 in the cecal ligation and puncture\u2013induced septic model in mice. The activation of CB2 signaling with HU308 led to decreased survival rates and more severe lung injury in septic mice, and lower IL-10 levels in peritoneal lavage fluid were observed in the CB2 agonist group. The mice with conditional knockout of CB2-encoding gene CNR2 in CD4+ T cells (CD4 Cre CNR2fl\/fl) improved survival, enhanced IL-10 production, and ameliorated pulmonary damage in the sepsis model after CB2 activation. In addition, double-knockout of the CNR2 gene (Lyz2 Cre CD4 Cre CNR2fl\/fl) decreased the susceptibility to sepsis compared with Lyz2 Cre CNR2fl\/fl mice. Mechanistically, the blockade of IL-10 with the anti\u2013IL-10 Ab abolished its protection in CD4 Cre CNR2fl\/fl mice. In accordance with the animal study, in vitro results revealed that the lack of CNR2 in CD4+ cells elevated IL-10 production, and CB2 activation inhibited CD4+ T cell\u2013derived IL-10 production. Furthermore, in the clinical environment, septic patients expressed enhanced CB2 mRNA levels compared with healthy donors in PBMCs, and their CB2 expression was inversely correlated with IL-10. These results suggested that the activation of CD4+ T cell\u2013derived CB2 increased susceptibility to sepsis through inhibiting IL-10 production.<\/jats:p>","DOI":"10.4049\/jimmunol.2101015","type":"journal-article","created":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T19:20:52Z","timestamp":1657740052000},"page":"2515-2522","source":"Crossref","is-referenced-by-count":11,"title":["Activation of CD4+ T Cell\u2013Derived Cannabinoid Receptor 2 Signaling Exacerbates Sepsis via Inhibiting IL-10"],"prefix":"10.1093","volume":"208","author":[{"given":"Jincheng","family":"Chen","sequence":"first","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases, Guangdong Provincial Clinical Research Center for Tuberculosis, The Third People\u2019s Hospital of Shenzhen, Southern University of Science and Technology , Shenzhen,","place":["China"]},{"name":"Savaid Medical School, University of Chinese Academy of Sciences , Beijing,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fuxiang","family":"Wang","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases, Guangdong Provincial Clinical Research Center for Tuberculosis, The Third People\u2019s Hospital of Shenzhen, Southern University of Science and Technology , Shenzhen,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Su","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases, Guangdong Provincial Clinical Research Center for Tuberculosis, The Third People\u2019s Hospital of Shenzhen, Southern University of Science and Technology , Shenzhen,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiao","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine, The Baoan People\u2019s Hospital of Shenzhen, Shenzhen University , Shenzhen,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Xu","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases, Guangdong Provincial Clinical Research Center for Tuberculosis, The Third People\u2019s Hospital of Shenzhen, Southern University of Science and Technology , Shenzhen,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tengfei","family":"Zhu","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases, Guangdong Provincial Clinical Research Center for Tuberculosis, The Third People\u2019s Hospital of Shenzhen, Southern University of Science and Technology , Shenzhen,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Peng","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases, Guangdong Provincial Clinical Research Center for Tuberculosis, The Third People\u2019s Hospital of Shenzhen, Southern University of Science and Technology , Shenzhen,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fulan","family":"Cen","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases, Guangdong Provincial Clinical Research Center for Tuberculosis, The Third People\u2019s Hospital of Shenzhen, Southern University of Science and Technology , Shenzhen,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2978-311X","authenticated-orcid":false,"given":"Fang","family":"Li","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases, Guangdong Provincial Clinical Research Center for Tuberculosis, The Third People\u2019s Hospital of Shenzhen, Southern University of Science and Technology , Shenzhen,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaoqin","family":"Wang","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases, Guangdong Provincial Clinical Research Center for Tuberculosis, The Third People\u2019s Hospital of Shenzhen, Southern University of Science and Technology , Shenzhen,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4301-4640","authenticated-orcid":false,"given":"Carl G","family":"Feng","sequence":"additional","affiliation":[{"name":"Infectious, Immunity and Inflammation, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney , Sydney,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6524-8777","authenticated-orcid":false,"given":"Zhinan","family":"Yin","sequence":"additional","affiliation":[{"name":"Biomedical Translational Research Institute, Faculty of Medical Science, Jinan University , Guangzhou,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6335-3346","authenticated-orcid":false,"given":"Yingxia","family":"Liu","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases, Guangdong Provincial Clinical Research Center for Tuberculosis, The Third People\u2019s Hospital of Shenzhen, Southern University of Science and Technology , Shenzhen,","place":["China"]},{"name":"Savaid Medical School, University of Chinese Academy of Sciences , 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