{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T12:05:36Z","timestamp":1785326736768,"version":"3.55.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2023,4,14]],"date-time":"2023-04-14T00:00:00Z","timestamp":1681430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["CRC 841"],"award-info":[{"award-number":["CRC 841"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>IL-6 plays a fundamental role in T cell differentiation and is strictly controlled by surface expression and shedding of IL-6R. IL-6 also acts on other cells that might affect T cell maturation. To study the impact of cell-autonomous and uncontrolled IL-6 signaling in T cells, we generated mice with a constitutively active IL-6R gp130 chain (Lgp130) expressed either in all T cells (Lgp130 \u00d7 CD4Cre mice) or inducible in CD4+ T cells (Lgp130 \u00d7 CD4CreERT2 mice). Lgp130 \u00d7 CD4Cre mice accumulated activated T cells, including TH17 cells, in the lung, resulting in severe inflammation. Tamoxifen treatment of Lgp130 \u00d7 CD4CreERT2 mice caused Lgp130 expression in 40\u201350% of CD4+ T cells, but mice developed lung disease only after several months. Lgp130+ CD4+ T cells were also enriched for TH17 cells; however, there was concomitant expansion of Lgp130\u2212 regulatory T cells, which likely restricted pathologic Lgp130+ T cells. In vitro, constitutive gp130 signaling in T cells enhanced but was not sufficient for TH17 cell differentiation. Augmented TH17 cell development of Lgp130+ T cells was also observed in Lgp130 \u00d7 CD4CreERT2 mice infected with Staphylococcus aureus, but gp130 activation did not interfere with formation of TH1 cells against Listeria monocytogenes. Lgp130+ CD4+ T cells acquired a memory T cell phenotype and persisted in high numbers as a polyclonal T cell population in lymphoid and peripheral tissues, but we did not observe T cell lymphoma formation. In conclusion, cell-autonomous gp130 signaling alters T cell differentiation. Although gp130 signaling is not sufficient for TH17 cell differentiation, it still promotes accumulation of activated T cells in the lung that cause tissue inflammation.<\/jats:p>","DOI":"10.4049\/jimmunol.2200461","type":"journal-article","created":{"date-parts":[[2023,4,14]],"date-time":"2023-04-14T14:28:01Z","timestamp":1681482481000},"page":"1717-1727","source":"Crossref","is-referenced-by-count":6,"title":["Cell-Autonomous Constitutive gp130 Signaling in T Cells Amplifies TH17 Cell Responses and Causes Severe Lung Inflammation"],"prefix":"10.1093","volume":"210","author":[{"given":"Lisa Charlotte","family":"Heinig","sequence":"first","affiliation":[{"name":"Institute for Immunology, University Medical Center Hamburg\u2013Eppendorf , Hamburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily Valentina Madelaine","family":"Huth","sequence":"additional","affiliation":[{"name":"Institute for Immunology, University Medical Center Hamburg\u2013Eppendorf , Hamburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karsten","family":"Yan","sequence":"additional","affiliation":[{"name":"Institute for Immunology, University Medical Center Hamburg\u2013Eppendorf , Hamburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neele","family":"Schumacher","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Christian Albrechts University Kiel , Kiel,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8579-7236","authenticated-orcid":false,"given":"Mikolaj","family":"Nawrocki","sequence":"additional","affiliation":[{"name":"I. Department of Medicine, University Medical Center Hamburg\u2013Eppendorf , Hamburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels Christian","family":"Lory","sequence":"additional","affiliation":[{"name":"Institute for Immunology, University Medical Center Hamburg\u2013Eppendorf , Hamburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Bradtke","sequence":"additional","affiliation":[{"name":"Institute for Immunology, University Medical Center Hamburg\u2013Eppendorf , Hamburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3338-5536","authenticated-orcid":false,"given":"Tabea","family":"Bertram","sequence":"additional","affiliation":[{"name":"Institute for Immunology, University Medical Center Hamburg\u2013Eppendorf , Hamburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0097-3163","authenticated-orcid":false,"given":"Guido","family":"Rattay","sequence":"additional","affiliation":[{"name":"I. Department of Medicine, University Medical Center Hamburg\u2013Eppendorf , Hamburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Schmid","sequence":"additional","affiliation":[{"name":"Institute for Immunology, University Medical Center Hamburg\u2013Eppendorf , Hamburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9325-8227","authenticated-orcid":false,"given":"Samuel","family":"Huber","sequence":"additional","affiliation":[{"name":"I. Department of Medicine, University Medical Center Hamburg\u2013Eppendorf , Hamburg,","place":["Germany"]},{"name":"Hamburg Center for Translational Immunology, University Medical Center Hamburg\u2013Eppendorf , Hamburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4053-1474","authenticated-orcid":false,"given":"Thorsten","family":"Wiech","sequence":"additional","affiliation":[{"name":"Institute for Pathology, University Medical Center Hamburg\u2013Eppendorf , Hamburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1072-7495","authenticated-orcid":false,"given":"Dirk","family":"Schmidt-Arras","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Christian Albrechts University Kiel , Kiel,","place":["Germany"]},{"name":"Department of Biosciences and Medical Biology, Paris Lodron University Salzburg , Salzburg,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7519-3279","authenticated-orcid":false,"given":"Stefan","family":"Rose-John","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Christian Albrechts University Kiel , Kiel,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6166-4191","authenticated-orcid":false,"given":"Hans-Willi","family":"Mittr\u00fccker","sequence":"additional","affiliation":[{"name":"Institute for Immunology, University Medical Center Hamburg\u2013Eppendorf , Hamburg,","place":["Germany"]},{"name":"Hamburg Center for Translational Immunology, University Medical Center Hamburg\u2013Eppendorf , Hamburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,4,14]]},"reference":[{"key":"2025021008061116300_r1","doi-asserted-by":"crossref","first-page":"a028415","DOI":"10.1101\/cshperspect.a028415","article-title":"Interleukin-6 family cytokines","volume":"10","author":"Rose-John","year":"2018","journal-title":"Cold Spring Harb. 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