{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T19:12:23Z","timestamp":1785006743816,"version":"3.55.0"},"reference-count":45,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T00:00:00Z","timestamp":1654819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Dutch Heart Foundation","award":["2016T052 (DvU\/MK)"],"award-info":[{"award-number":["2016T052 (DvU\/MK)"]}]},{"name":"Ferrer pharmaceuticals","award":["2016T052 (DvU\/MK)"],"award-info":[{"award-number":["2016T052 (DvU\/MK)"]}]},{"name":"Actelion Pharmaceuticals","award":["2016T052 (DvU\/MK)"],"award-info":[{"award-number":["2016T052 (DvU\/MK)"]}]},{"name":"Pulmonary Hypertension Patients Association (TK)","award":["2016T052 (DvU\/MK)"],"award-info":[{"award-number":["2016T052 (DvU\/MK)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pulmonary arterial hypertension (PAH) is rare disease that is categorized as idiopathic (IPAH) when no underlying cause can be identified. Lungs of most patients with IPAH contain increased numbers of T cells and dendritic cells (DCs), suggesting involvement of the immune system in its pathophysiology. However, our knowledge on circulating immune cells in IPAH is rather limited. We used flow cytometry to characterize peripheral blood DCs and T cells in treatment-naive IPAH patients, compared with connective-tissue disease-PAH (CTD-PAH) patients and healthy controls (HCs). At diagnosis, T-helper (Th) cells of IPAH patients were less capable of producing TNF\u03b1, IFN\u03b3, IL-4 and IL-17 compared to HCs. IPAH patients showed a decreased frequency of Th2 cells and significantly enhanced expression of the CTLA4 checkpoint molecule in naive CD4+ T cells and both naive and memory CD8+ T cells. Frequencies and surface marker expression of circulating DCs and monocytes were essentially comparable between IPAH patients and HCs. Principal component analysis (PCA) separated IPAH patients\u2014but not CTD-PAH patients\u2014from HCs, based on T-cell cytokine profiles. At 1-year follow-up, the frequencies of IL-17+ production by memory CD4+ T cells were increased in IPAH patients and accompanied by increased proportions of Th17 and Tc17 cells, as well as decreased CTLA4 expression. Treatment-naive IPAH patients displayed a unique T-cell phenotype that was different from CTD-PAH patients and was characterized by reduced cytokine-producing capacity. These findings point to involvement of adaptive immune responses in IPAH, which may have an implication for the development of therapeutic interventions.<\/jats:p>","DOI":"10.3390\/ijms23126508","type":"journal-article","created":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T10:25:12Z","timestamp":1654856712000},"page":"6508","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Peripheral Blood T Cells of Patients with IPAH Have a Reduced Cytokine-Producing Capacity"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4120-8900","authenticated-orcid":false,"given":"Denise","family":"van Uden","sequence":"first","affiliation":[{"name":"Department of Pulmonary Medicine, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Koudstaal","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer A. C.","family":"van Hulst","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madelief","family":"Vink","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menno","family":"van Nimwegen","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon M.","family":"van den Toorn","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prewesh P.","family":"Chandoesing","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemien E.","family":"van den Bosch","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirjam","family":"Kool","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudi W.","family":"Hendriks","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1519-8147","authenticated-orcid":false,"given":"Karin A.","family":"Boomars","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1801913","DOI":"10.1183\/13993003.01913-2018","article-title":"Haemodynamic definitions and updated clinical classification of pulmonary hypertension","volume":"53","author":"Simonneau","year":"2019","journal-title":"Eur. 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