{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T14:01:50Z","timestamp":1793109710489,"version":"4.5.0"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"vor","delay-in-days":1554,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Pulmonary sarcoidosis is generally presumed to be a T-helper cell type 1\u2013 and macrophage-driven disease. However, mouse models have recently revealed that chronically inflamed lung tissue can also comprise T follicular helper (Tfh)-like cells and represents a site of active T-cell\/B-cell cooperation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To assess the role of pulmonary Tfh- and germinal center\u2013like lymphocytes in sarcoidosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>BAL fluid, lung tissue, and peripheral blood samples from patients with sarcoidosis were analyzed by flow cytometry, immunohistology, RNA sequencing, and in vitro T-cell\/B-cell cooperation assays for phenotypic and functional characterization of germinal center\u2013like reactions in inflamed tissue.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>We identified a novel population of Tfh-like cells characterized by high expression of the B helper molecules CD40L and IL-21 in BAL of patients with sarcoidosis. Transcriptome analysis further confirmed a phenotype that was both Tfh-like and tissue resident. BAL T cells provided potent help for B cells to differentiate into antibody-producing cells. In lung tissue, we observed large peribronchial infiltrates with T and B cells in close contact, and many IgA+ plasmablasts. Most clusters were nonectopic; that is, they did not contain follicular dendritic cells. Patients with sarcoidosis also showed elevated levels of PD-1high CXCR5\u2212 CD40Lhigh ICOShigh Tfh-like cells, but not classical CXCR5+ Tfh cells, in the blood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Active T-cell\/B-cell cooperation and local production of potentially pathogenic antibodies in the inflamed lung represents a novel pathomechanism in sarcoidosis and should be considered from both diagnostic and therapeutic perspectives.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202012-4423oc","type":"journal-article","created":{"date-parts":[[2021,9,17]],"date-time":"2021-09-17T18:13:02Z","timestamp":1631902382000},"page":"1403-1417","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":38,"title":["Follicular Helper\u2013like T Cells in the Lung Highlight a Novel Role of B Cells in Sarcoidosis"],"prefix":"10.1093","volume":"204","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1435-8121","authenticated-orcid":false,"given":"Laura","family":"Bauer","sequence":"first","affiliation":[{"name":"Institute of Immunology and"},{"name":"Chronic Immune Reactions and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6708-1667","authenticated-orcid":false,"given":"Lisa Jasmin","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Chronic Immune Reactions and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0354-5252","authenticated-orcid":false,"given":"Sarah M.","family":"Volkers","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Respiratory Medicine, Charit\u00e9 University Medicine Berlin, Corporate Member of Free University of Berlin, Humboldt University of Berlin, and Berlin Institute of Health, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6097-5422","authenticated-orcid":false,"given":"Frederik","family":"Heinrich","sequence":"additional","affiliation":[{"name":"Therapeutic Gene Regulation, German Rheumatism Research Centre, A Leibniz Institute, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8015-6907","authenticated-orcid":false,"given":"Mir-Farzin","family":"Mashreghi","sequence":"additional","affiliation":[{"name":"Therapeutic Gene Regulation, German Rheumatism Research Centre, A Leibniz Institute, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0938-2469","authenticated-orcid":false,"given":"Clemens","family":"Ruppert","sequence":"additional","affiliation":[{"name":"Universities of Giessen and Marburg Lung Center, Giessen, Germany; 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