{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T15:19:02Z","timestamp":1778253542569,"version":"3.51.4"},"reference-count":0,"publisher":"American Society of Hematology","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:p>Peripheral T-cell lymphomas (PTCL) - especially angioimmunoblastic (AITL) and follicular TCL - have a dismal prognosis due to lack of efficient therapies, and patients` symptoms are often dominated by an inflammatory phenotype including fever, night sweats, weight loss and skin rash. In this study, we investigated the role of inflammatory granulocytes and activated cytokine signaling on PTCL-TFH (T-follicular helper type) disease progression and symptoms. We show, that ITK-SYK driven murine PTCLs and primary human PTCL-TFH xenografts both induce inflammation in mice including murine neutrophil expansion and massive cytokine release. Granulocyte\/lymphoma interactions were mediated by positive autoregulatory cytokine loops involving INF-\u03b3 (CD4+malignant T-cells) and IL-6 (activated granulocytes), ultimately inducing broad JAK kinase activation (Jak1\/2\/3, Tyk2) in both cell types. Depletion of inflammatory granulocytes via antibodies (Ly6G), genetic granulocyte depletion (LyzM-Cre\/MCL1flox\/flox) or the deletion of IL-6 within microenvironmental cells blocked inflammatory symptoms, reduced lymphoma infiltration and enhanced mouse survival. Furthermore, unselective JAK kinase inhibitors (ruxolitinib) inhibited both, TCL progression and granulocyte activation in various PTCL mouse models. Our results support the important role of granulocyte-driven inflammation, cytokine-induced granulocyte\/CD4+ TCL interactions and the requirement of an intact JAK\/STAT signaling pathway for PTCL-TFH development, and support broad JAK kinase inhibition as an effective treatment strategy in early disease stages.<\/jats:p>","DOI":"10.1182\/blood.2022015653","type":"journal-article","created":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T21:04:15Z","timestamp":1674680655000},"update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":8,"title":["Activated granulocytes and inflammatory cytokine signaling drive T-cell lymphoma progression and disease symptoms"],"prefix":"10.1182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1102-9629","authenticated-orcid":false,"given":"Amelie","family":"Jaeger","sequence":"first","affiliation":[{"name":"University Medical Center Freiburg, Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sudheer Madan Mohan","family":"Gambheer","sequence":"additional","affiliation":[{"name":"University Medical Center Freiburg, Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyang","family":"Sun","sequence":"additional","affiliation":[{"name":"University Medical Center Freiburg, Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dmitry","family":"Chernyakov","sequence":"additional","affiliation":[{"name":"University of Halle, Halle, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oleksandra","family":"Skorobohatko","sequence":"additional","affiliation":[{"name":"University of Halle, Halle, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas M.","family":"Mack","sequence":"additional","affiliation":[{"name":"University Medical Center Freiburg, Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Kissel","sequence":"additional","affiliation":[{"name":"University Medical Center Freiburg"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dietmar","family":"Pfeifer","sequence":"additional","affiliation":[{"name":"University Clinics Medical Center, Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Zeiser","sequence":"additional","affiliation":[{"name":"University Medical Center Freiburg, Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Fisch","sequence":"additional","affiliation":[{"name":"Freiburg University Hospital, Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5389-9481","authenticated-orcid":false,"given":"Geoffroy","family":"Andrieux","sequence":"additional","affiliation":[{"name":"Institute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany, Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9200-5455","authenticated-orcid":false,"given":"Daniela","family":"Br\u00e4uer-Hartmann","sequence":"additional","affiliation":[{"name":"Martin Luther University Halle-Wittenberg, Halle (Saale), Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcus","family":"Bauer","sequence":"additional","affiliation":[{"name":"Martin Luther University Halle-Wittenberg, Halle an der Saale, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susann","family":"Schulze","sequence":"additional","affiliation":[{"name":"University Hospital of Halle (Saale), Halle (Saale), Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3090-7442","authenticated-orcid":false,"given":"Marie","family":"Follo","sequence":"additional","affiliation":[{"name":"University Medical Center Freiburg, Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3670-0602","authenticated-orcid":false,"given":"Melanie","family":"Boerries","sequence":"additional","affiliation":[{"name":"Institute of Medical Bioinformatics and Systems Medicine, Medical Center - University ofer Freiburg, Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9593-8947","authenticated-orcid":false,"given":"Nikolas","family":"von Bubnoff","sequence":"additional","affiliation":[{"name":"Universit\u00e4tsklinikum Schleswig-Holstein, Campus L\u00fcbeck, L\u00fcbeck, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4699-3805","authenticated-orcid":false,"given":"Cornelius","family":"Miething","sequence":"additional","affiliation":[{"name":"DKTK Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jose Villacorta","family":"Hidalgo","sequence":"additional","affiliation":[{"name":"University Halle-Wittenberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudius","family":"Klein","sequence":"additional","affiliation":[{"name":"University Medical Center Freiburg, Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8724-9348","authenticated-orcid":false,"given":"Thomas","family":"Weber","sequence":"additional","affiliation":[{"name":"Martin-Luther-University Halle-Wittenberg, Halle, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Wickenhauser","sequence":"additional","affiliation":[{"name":"University Hospital of Halle, Halle \/ Saale, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mascha","family":"Binder","sequence":"additional","affiliation":[{"name":"Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Dierks","sequence":"additional","affiliation":[{"name":"Martin-Luther University Halle-Wittenberg, Halle, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"234","published-online":{"date-parts":[[2023,1,25]]},"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/doi\/10.1182\/blood.2022015653\/2030915\/blood.2022015653.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/doi\/10.1182\/blood.2022015653\/2030915\/blood.2022015653.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T21:04:16Z","timestamp":1674680656000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/doi\/10.1182\/blood.2022015653\/494232\/Activated-granulocytes-and-inflammatory-cytokine"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,25]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1182\/blood.2022015653","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,25]]},"article-number":"blood.2022015653"}}