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To investigate essential mechanisms that are linked toward a constitutively activated gp130 signaling, we generated and characterized a mouse model that reflects a constitutive and cytokine-independent activation of JAK\/STAT3 signaling by Lgp130 in CD4- and CD8-positive T cells. Lgp130 is an engineered form of gp130 in which dimerization and activation are forced by a leucine zipper. T cell\u2013specific Lgp130 activation resulted in massive phenotypical abnormalities, including splenomegaly, lymphadenopathy, and an upregulation of innate immune system components shown by hyperinflammatory signatures in several organs. Moreover, T cell\u2013restricted expression of Lgp130 resulted in increased numbers of cytotoxic and regulatory T cells, especially in lymph nodes. Consistent with this, we found an elevated platelet production and increase in megakaryocytes in the spleen and bone marrow that are causative for an acute thrombocytosis accompanied by anemia. Due to a shortened life span of T cell\u2013specific Lgp130 mice, we could also show that next to an overall increase in regulatory cell-cycle genes, an activation of p53 and increased expression of p21 provide evidence for a senescence-like phenotype. Together, these data suggest that T cell\u2013restricted gp130 activation is not only involved in autoimmune processes but also in senescence-associated aging. Therefore, Lgp130 expression in T cells might be a suitable model to study inflammation and disease.<\/jats:p>","DOI":"10.4049\/jimmunol.2200788","type":"journal-article","created":{"date-parts":[[2023,4,14]],"date-time":"2023-04-14T14:28:00Z","timestamp":1681482480000},"page":"1641-1652","source":"Crossref","is-referenced-by-count":7,"title":["Constitutive Activation of gp130 in T Cells Results in Senescence and Premature Aging"],"prefix":"10.1093","volume":"210","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-8742-3259","authenticated-orcid":false,"given":"Puyan","family":"Rafii","sequence":"first","affiliation":[{"name":"Institute of Biochemistry and Molecular Biology II, Medical Faculty, Heinrich-Heine-University , D\u00fcsseldorf,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9989-4571","authenticated-orcid":false,"given":"Friedrich","family":"Reusswig","sequence":"additional","affiliation":[{"name":"Clinic 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Heinrich-Heine-University , D\u00fcsseldorf,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5964-0385","authenticated-orcid":false,"given":"Simone","family":"Gorressen","sequence":"additional","affiliation":[{"name":"Institute for Pharmacology, Heinrich-Heine-University , D\u00fcsseldorf,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8608-2033","authenticated-orcid":false,"given":"Christina","family":"Alter","sequence":"additional","affiliation":[{"name":"Institute of Molecular Cardiology, Medical Faculty, Heinrich-Heine-University , D\u00fcsseldorf,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7742-2768","authenticated-orcid":false,"given":"J\u00fcrgen","family":"Schrader","sequence":"additional","affiliation":[{"name":"Institute of Molecular Cardiology, Medical Faculty, Heinrich-Heine-University , D\u00fcsseldorf,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8528-0122","authenticated-orcid":false,"given":"Diran","family":"Herebian","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Neonatology and Pediatric Cardiology, Medical Faculty, Heinrich-Heine-University D\u00fcsseldorf , D\u00fcsseldorf,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6675-5313","authenticated-orcid":false,"given":"Doreen M","family":"Floss","sequence":"additional","affiliation":[{"name":"Institute of 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