{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T14:44:38Z","timestamp":1793371478008,"version":"4.5.0"},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T00:00:00Z","timestamp":1698192000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Centre","doi-asserted-by":"publisher","award":["2016\/21\/B\/NZ5\/01397"],"award-info":[{"award-number":["2016\/21\/B\/NZ5\/01397"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,2,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Tumour necrosis factor \u03b1 (TNF-\u03b1) represents a classical pro-inflammatory cytokine, and its increased levels positively correlate with the severity of many cardiovascular diseases. Surprisingly, some heart failure patients receiving high doses of anti-TNF-\u03b1 antibodies showed serious health worsening. This work aimed to examine the role of TNF-\u03b1 signalling on the development and progression of myocarditis and heart-specific autoimmunity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>Mice with genetic deletion of TNF-\u03b1 (Tnf+\/\u2212 and Tnf\u2212\/\u2212) and littermate controls (Tnf+\/+) were used to study myocarditis in the inducible and the transgenic T cell receptor (TCRM) models. Tnf+\/\u2212 and Tnf\u2212\/\u2212 mice immunized with \u03b1-myosin heavy chain peptide (\u03b1MyHC) showed reduced myocarditis incidence, but the susceptible animals developed extensive inflammation in the heart. In the TCRM model, defective TNF-\u03b1 production was associated with increased mortality at a young age due to cardiomyopathy and cardiac fibrosis. We could confirm that TNF-\u03b1 as well as the secretome of antigen-activated heart-reactive effector CD4+ T (Teff) cells effectively activated the adhesive properties of cardiac microvascular endothelial cells (cMVECs). Our data suggested that TNF-\u03b1 produced by endothelial in addition to Teff cells promoted leucocyte adhesion to activated cMVECs. Analysis of CD4+ T lymphocytes from both models of myocarditis showed a strongly increased fraction of Teff cells in hearts, spleens, and in the blood of Tnf+\/\u2212 and Tnf\u2212\/\u2212 mice. Indeed, antigen-activated Tnf\u2212\/\u2212 Teff cells showed prolonged long-term survival and TNF-\u03b1 cytokine-induced cell death of heart-reactive Teff.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>TNF-\u03b1 signalling promotes myocarditis development by activating cardiac endothelial cells. However, in the case of established disease, TNF-\u03b1 protects from exacerbating cardiac inflammation by inducing activation-induced cell death of heart-reactive Teff. These data might explain the lack of success of standard anti-TNF-\u03b1 therapy in heart failure patients and open perspectives for T cell\u2013targeted approaches.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvad158","type":"journal-article","created":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T21:10:51Z","timestamp":1698268251000},"page":"82-94","source":"Crossref","is-referenced-by-count":57,"title":["TNF-\u03b1 protects from exacerbated myocarditis and cardiac death by suppressing expansion of activated heart-reactive CD4+ T cells"],"prefix":"10.1093","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9159-6169","authenticated-orcid":false,"given":"Filip","family":"Rolski","sequence":"first","affiliation":[{"name":"Department of Clinical Immunology, Jagiellonian University Medical College , Wielicka 265 , Cracow 30-663, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4707-9126","authenticated-orcid":false,"given":"Karolina","family":"Tkacz","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Jagiellonian University Medical College , Wielicka 265 , Cracow 30-663, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazimierz","family":"W\u0119glarczyk","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Jagiellonian University Medical College , Wielicka 265 , Cracow 30-663, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grzegorz","family":"Kwiatkowski","sequence":"additional","affiliation":[{"name":"Jagiellonian Centre for Experimental Therapeutics , Jagiellonian University, Cracow , Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawe\u0142","family":"Pelczar","sequence":"additional","affiliation":[{"name":"Center for Transgenic Models, University of Basel , Basel , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Ja\u017awa-Kusior","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology, Jagiellonian University , Cracow , Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0182-6501","authenticated-orcid":false,"given":"Anna","family":"Bar","sequence":"additional","affiliation":[{"name":"Jagiellonian Centre for Experimental Therapeutics , Jagiellonian University, Cracow , Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela M","family":"Kuster","sequence":"additional","affiliation":[{"name":"Clinic of Cardiology, University Hospital Basel , Basel , Switzerland"},{"name":"Department of Biomedicine, University Hospital and University of Basel , Basel , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Ch\u0142opicki","sequence":"additional","affiliation":[{"name":"Jagiellonian Centre for Experimental Therapeutics , Jagiellonian University, Cracow , Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3904-5412","authenticated-orcid":false,"given":"Maciej","family":"Siedlar","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Jagiellonian University Medical College , Wielicka 265 , Cracow 30-663, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3788-4594","authenticated-orcid":false,"given":"Gabriela","family":"Kania","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, University Hospital Zurich, University of Zurich , Wagistrasse 14, 8952 Schlieren , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2521-3232","authenticated-orcid":false,"given":"Przemys\u0142aw","family":"B\u0142yszczuk","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Jagiellonian University Medical College , Wielicka 265 , Cracow 30-663, Poland"},{"name":"Department of Rheumatology, University Hospital Zurich, University of Zurich , Wagistrasse 14, 8952 Schlieren , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,10,25]]},"container-title":["Cardiovascular Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/cardiovascres\/advance-article-pdf\/doi\/10.1093\/cvr\/cvad158\/53000416\/cvad158.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cardiovascres\/article-pdf\/120\/1\/82\/56773755\/cvad158.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cardiovascres\/article-pdf\/120\/1\/82\/56773755\/cvad158.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T23:28:59Z","timestamp":1709076539000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cardiovascres\/article\/120\/1\/82\/7329956"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,25]]},"references-count":0,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,10,25]]},"published-print":{"date-parts":[[2024,2,27]]}},"URL":"https:\/\/doi.org\/10.1093\/cvr\/cvad158","relation":{},"ISSN":["0008-6363","1755-3245"],"issn-type":[{"value":"0008-6363","type":"print"},{"value":"1755-3245","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,1]]},"published":{"date-parts":[[2023,10,25]]}}}