{"id":13811,"date":"2023-03-06T10:56:00","date_gmt":"2023-03-06T10:56:00","guid":{"rendered":"https:\/\/www.drfz.de\/neuigkeiten\/das-alarmin-il-33-stimuliert-tcf1-cd8-t-zellen-bei-chronischen-infektionen\/"},"modified":"2025-03-11T13:06:26","modified_gmt":"2025-03-11T13:06:26","slug":"das-alarmin-il-33-stimuliert-tcf1-cd8-t-zellen-bei-chronischen-infektionen","status":"publish","type":"post","link":"https:\/\/www.drfz.de\/en\/neuigkeiten\/das-alarmin-il-33-stimuliert-tcf1-cd8-t-zellen-bei-chronischen-infektionen\/","title":{"rendered":"The alarmin IL-33 promotes Tcf-1+ CD8+ T cells in chronic viral infections"},"content":{"rendered":"\n

Chronic CD8+<\/sup> T cell responses to viral infections and cancer are maintained by a distinct subset of stem-like CD8+<\/sup> T cells (CD8+<\/sup>SL) characterized by expression of the transcription factor TCF-1 and the inhibitory receptor PD-1. In contrast to terminally differentiated effector cells, CD8+<\/sup>SL maintain a high self-renewing capacity and robust expansion potential thus ensuring long-term T cell population maintenance under conditions of chronic antigen exposure. While recent studies have shown that CD8+<\/sup>SL are critical mediators of antitumoral T cell responses following immune checkpoint inhibition, the signals that control formation and maintenance of Tcf-1+<\/sup> CD8+<\/sup>SL remained largely undefined.<\/p>\n\n\n\n

A joint study by Daniel Pinschewer\u2019s group at the University of Basel and Max L\u00f6hning`s group at the DRFZ and Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, has now identified the alarmin IL-33 as a molecule essential for the expansion and stem-like functioning of CD8+<\/sup>SL in mice chronically infected with lymphocytic choriomeningitis virus (LCMV). By signaling through its receptor ST2, IL-33 was shown to positively regulate the expression of Tcf7<\/em> (encoding TCF-1), thus counterbalancing the type-1 interferon-mediated loss of this stemness-promoting transcription factor. Further, the research team demonstrated that IL-33 signals received early during infection broadly augmented chromatin accessibility in CD8+<\/sup>SL thus imprinting an epigenetic signature that ensures high self-renewal capacity and warrants sustainable antiviral CD8+ T cell responses to chronic viral infection. The important role of IL-33-ST2 signaling for CD8+<\/sup>SL generation may help to understand the beneficial effects of IL-33 blockade in T cell-driven inflammatory diseases and provides a rationale for ongoing efforts to harness alarmin signaling in tumor immunotherapy.<\/p>\n\n\n\n

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Marx AF, Kallert SM, Brunner TM, Villegas JA, Geier F, Fixemer J, Abreu-Mota T, Reuther P, Bonilla WV, Fadejeva J, Kreutzfeldt M, Wagner I, Frey-Wagner I, Wagner I, Aparicio-Domingo P, Scarpellino L, Charmoy M, Utzschneider DT, Hagedorn C, Lu M, Cornille K, Stauffer K, Kreppel F, Merkler D, Zehn D, Held W, Luther SA, L\u00f6hning M, Pinschewer DD.<\/div>\n \n
\n The alarmin interleukin-33 promotes the expansion and preserves the stemness of Tcf-1(+) CD8(+) T cells in chronic viral infection.<\/a>\n <\/div>\n\n
Immunity. 2023 Apr 11;56(4):813-828.e10. doi: 10.1016\/j.immuni.2023.01.029. Epub 2023 Feb 20. PMID: 36809763.<\/div>\n <\/div>\n \n <\/article>\n <\/div>\n \n <\/div>\n\n \n <\/div>\n\n\n <\/div>\n <\/section>\n\n\n\n\n
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\n \n Press release by the cooperation partners, University Basel <\/a>\n\n The marathon runners of the immune system<\/span>\n \n \n <\/span>\n <\/a>\n <\/div>\n <\/div>\n <\/div>\n <\/div>\n <\/section>\n\n\n\n\n
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Prof. Dr. Max L\u00f6hning<\/h2>\n
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\n Programme Area 3, PA 3 \u2013 Systems Rheumatology <\/p>\n

\n Group leader: Pitzer Laboratory of Osteoarthritis Research <\/p>\n Liaison working group with Charit\u00e9 – Rheumatology and Clinical Immunology<\/p>\n <\/div>\n <\/div>\n\n

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loehning@drfz.de<\/a><\/p>\n <\/div>\n Prof. Dr. Max L\u00f6hning<\/span><\/a>\n<\/article> <\/div>\n <\/div>\n <\/section>\n","protected":false},"excerpt":{"rendered":"

Chronic CD8+ T cell responses to viral infections and cancer are maintained by a distinct subset of stem-like CD8+ T cells (CD8+SL) characterized by expression of the\u2026<\/p>\n","protected":false},"author":9,"featured_media":11758,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[291,291],"tags":[472,425,496],"programme-area-tax":[181],"working-group-tax":[256],"class_list":{"0":"post-13811","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","6":"hentry","7":"category-publications","9":"tag-loehning","10":"tag-pitzer-lab-of-osteoarthritis-research","11":"tag-program-area-3","12":"programme-area-tax-programme-area-3","13":"working-group-tax-pitzer-laboratory-of-osteoarthritis-research-en"},"acf":[],"yoast_head":"\nThe alarmin IL-33 promotes Tcf-1+ CD8+ T cells in chronic viral infections - DRFZ<\/title>\n<meta name=\"robots\" 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