{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T04:00:18Z","timestamp":1793678418325,"version":"4.5.1"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T00:00:00Z","timestamp":1674432000000},"content-version":"vor","delay-in-days":516,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2021,8,25]],"date-time":"2021-08-25T00:00:00Z","timestamp":1629849600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2021,8,25]],"date-time":"2021-08-25T00:00:00Z","timestamp":1629849600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,3,25]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Sarcoidosis is a systemic inflammatory disease mainly affecting the lungs. The hallmark of sarcoidosis are granulomas that are surrounded by activated T cells, likely targeting the disease-inducing antigen. IFN\u03b3-producing Th1 and Th17.1 T cells are elevated in sarcoidosis and associate with disease progression. Monocytes and dendritic cells (DCs) are antigen-presenting cells (APCs) and required for T cell activation. Several subsets of monocytes and DCs with different functions were identified in sarcoidosis. However, to what extent different monocyte and DC subsets can support activation and skewing of T cells in sarcoidosis is still unclear. In this study, we performed a transcriptional and functional side-by-side comparison of sorted monocytes and DCs from matched blood and bronchoalveolar lavage (BAL) fluid of sarcoidosis patients. Transcriptomic analysis of all subsets showed upregulation of genes related to T cell activation and antigen presentation in DCs compared with monocytes. Allogeneic T cell proliferation was higher after coculture with monocytes and DCs from blood compared with BAL and DCs induced more T cell proliferation compared with monocytes. After coculture, proliferating T cells showed high expression of the transcription factor Tbet and IFN\u03b3 production. We also identified Tbet and ROR\u03b3t coexpressing T cells that mainly produced IFN\u03b3. Our data show that DCs rather than monocytes from sarcoidosis patients have the ability to activate and polarize T cells towards Th1 and Th17.1 cells. This study provides a useful in vitro tool to better understand the contribution of monocytes and DCs to T cell activation and immunopathology in sarcoidosis.<\/jats:p>","DOI":"10.1002\/jlb.5a0321-162r","type":"journal-article","created":{"date-parts":[[2021,8,25]],"date-time":"2021-08-25T10:01:33Z","timestamp":1629885693000},"page":"857-866","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Pulmonary and blood dendritic cells from sarcoidosis patients more potently induce IFN\u03b3-producing Th1 cells compared with monocytes"],"prefix":"10.1093","volume":"111","author":[{"given":"Rico","family":"Lepzien","sequence":"first","affiliation":[{"name":"Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital , Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mu","family":"Nie","sequence":"additional","affiliation":[{"name":"Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital , Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo","family":"Czarnewski","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics, National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Stockholm University , Solna, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital , Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Yu","sequence":"additional","affiliation":[{"name":"Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital , Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avinash","family":"Ravindran","sequence":"additional","affiliation":[{"name":"Division of Respiratory Medicine, Department of Medicine Solna and Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital , Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna","family":"Kullberg","sequence":"additional","affiliation":[{"name":"Division of Respiratory Medicine, Department of Medicine Solna and Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital , Stockholm, Sweden"},{"name":"Department of Respiratory Medicine, Theme Inflammation and Infection, Karolinska University Hospital , Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Eklund","sequence":"additional","affiliation":[{"name":"Division of Respiratory Medicine, Department of Medicine Solna and Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital , Stockholm, Sweden"},{"name":"Department of Respiratory Medicine, Theme Inflammation and Infection, Karolinska University Hospital , Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Grunewald","sequence":"additional","affiliation":[{"name":"Division of Respiratory Medicine, Department of Medicine Solna and Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital , Stockholm, Sweden"},{"name":"Department of Respiratory Medicine, Theme Inflammation and Infection, Karolinska University Hospital , Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Smed-S\u00f6rensen","sequence":"additional","affiliation":[{"name":"Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital , Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,8,25]]},"reference":[{"key":"2023032109030146500_","doi-asserted-by":"crossref","first-page":"437","DOI":"10.3389\/fimmu.2013.00437","article-title":"Granuloma formation in pulmonary sarcoidosis","volume":"4","author":"Broos","year":"2013","journal-title":"Front Immunol"},{"key":"2023032109030146500_","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/s41572-019-0096-x","article-title":"Sarcoidosis","volume":"5","author":"Grunewald","year":"2019","journal-title":"Nat Rev Dis Prim"},{"key":"2023032109030146500_","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1136\/thx.2010.140319","article-title":"Sarcoidosis is a Th1\/Th17 multisystem disorder","volume":"66","author":"Facco","year":"2011","journal-title":"Thorax"},{"key":"2023032109030146500_","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1111\/cei.12403","article-title":"Higher levels of interleukin IL-17 and antigen-specific IL-17 responses in pulmonary sarcoidosis patients with L\u00f6fgren's syndrome","volume":"178","author":"Ostadkarampour","year":"2014","journal-title":"Clin Exp Immunol"},{"key":"2023032109030146500_","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1183\/13993003.00092-2016","article-title":"Expanded lung T-bet+RORgammaT+ CD4+ T-cells in sarcoidosis patients with a favourable disease phenotype","volume":"48","author":"Kaiser","year":"2016","journal-title":"Eur Respir J"},{"key":"2023032109030146500_","doi-asserted-by":"crossref","DOI":"10.1183\/13993003.01124-2017","article-title":"Increased T-helper 17.1 cells in sarcoidosis mediastinal lymph nodes","author":"Broos","year":"2018","journal-title":"Eur Respir J"},{"key":"2023032109030146500_","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1164\/rccm.201507-1499OC","article-title":"IFN-gamma-producing T-Helper 17.1 cells are increased in sarcoidosis and are more prevalent than T-helper type 1 cells","volume":"193","author":"Ramstein","year":"2016","journal-title":"Am J Respir Crit Care Med"},{"key":"2023032109030146500_","doi-asserted-by":"crossref","first-page":"e74","DOI":"10.1182\/blood-2010-02-258558","article-title":"Nomenclature of monocytes and dendritic cells in blood","volume":"116","author":"Ziegler-Heitbrock","year":"2010","journal-title":"Blood"},{"key":"2023032109030146500_","article-title":"Smed-S\u00f6rensen, A. (2021) Monocytes in sarcoidosis are potent TNF producers and predict disease outcome","author":"Lepzien","journal-title":"Eur Respir J"},{"key":"2023032109030146500_","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.semcdb.2015.03.011","article-title":"Dendritic cells and monocyte-derived cells: two complementary and integrated functional systems","volume":"41","author":"Schlitzer","year":"2015","journal-title":"Semin Cell Dev Biol"},{"key":"2023032109030146500_","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/j.cell.2018.09.009","article-title":"Lung single-cell signaling interaction map reveals basophil role in macrophage imprinting","volume":"175","author":"Cohen","year":"2018","journal-title":"Cell"},{"key":"2023032109030146500_","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1016\/j.immuni.2017.11.024","article-title":"Cellular differentiation of human monocytes is regulated by time-dependent interleukin-4 signaling and the transcriptional regulator NCOR2","volume":"47","author":"Sander","year":"2017","journal-title":"Immunity"},{"key":"2023032109030146500_","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/j.immuni.2016.02.017","article-title":"Yolk Sac macrophages, fetal liver, and adult monocytes can colonize an empty niche and develop into functional tissue-resident macrophages","volume":"44","author":"van de Laar","year":"2016","journal-title":"Immunity"},{"key":"2023032109030146500_","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.ccm.2015.08.016","article-title":"Cellular players in the immunopathogenesis of sarcoidosis","volume":"36","author":"Zissel","year":"2015","journal-title":"Clin Chest Med"},{"key":"2023032109030146500_","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/1465-9921-13-33","article-title":"Evidence for local dendritic cell activation in pulmonary sarcoidosis","volume":"13","author":"Ten Berge","year":"2012","journal-title":"Respir Res"},{"key":"2023032109030146500_","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1111\/j.1365-2249.2009.04046.x","article-title":"Functional analysis of dendritic cell-T cell interaction in sarcoidosis","volume":"159","author":"Kulakova","year":"2010","journal-title":"Clin Exp Immunol"},{"key":"2023032109030146500_","doi-asserted-by":"crossref","first-page":"4498","DOI":"10.4049\/jimmunol.1600071","article-title":"Dendritic cells and monocytes with distinct inflammatory responses reside in lung mucosa of healthy humans","volume":"196","author":"Baharom","year":"2016","journal-title":"J Immunol"},{"key":"2023032109030146500_","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1164\/rccm.201507-1376OC","article-title":"Flow cytometric analysis of mononuclear phagocytes in nondiseased human lung and lung-draining lymph nodes","volume":"193","author":"Desch","year":"2016","journal-title":"Am J Respir Crit Care Med"},{"key":"2023032109030146500_","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.4049\/jimmunol.1600777","article-title":"Transcriptional classification and functional characterization of human airway macrophage and dendritic cell subsets","volume":"198","author":"Patel","journal-title":"J Immunol"},{"key":"2023032109030146500_","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1002\/JLB.5A0718-280RR","article-title":"Mapping mononuclear phagocytes in blood, lungs, and lymph nodes of sarcoidosis patients","volume":"105","author":"Lepzien","year":"2019","journal-title":"J Leukocyte Biol"},{"key":"2023032109030146500_","doi-asserted-by":"crossref","first-page":"e43644","DOI":"10.1371\/journal.pone.0043644","article-title":"Bronchoalveolar lavage results are independent of season, age, gender and collection site","volume":"7","author":"Olsen","year":"2012","journal-title":"PLoS One"},{"key":"2023032109030146500_","first-page":"139","article-title":"edgeR: a Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics (Oxford, England)"},{"key":"2023032109030146500_","doi-asserted-by":"crossref","first-page":"W90","DOI":"10.1093\/nar\/gkw377","article-title":"Enrichr: a comprehensive gene set enrichment analysis web server 2016 update","volume":"44","author":"Kuleshov","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"2023032109030146500_","doi-asserted-by":"crossref","DOI":"10.1183\/13993003.021532018","article-title":"Moving target: shifting the focus to pulmonary sarcoidosis as an autoimmune spectrum disorder","volume":"54","author":"Kaiser","year":"2019","journal-title":"Eur Respir J"},{"key":"2023032109030146500_","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1055\/s-0037-1602380","article-title":"L\u00f6fgren's syndrome: diagnosis, management, and disease pathogenesis","volume":"38","author":"Karakaya","year":"2017","journal-title":"Semin Respir Crit Care Med"},{"key":"2023032109030146500_","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.jaut.2017.12.012","article-title":"Th17-lineage cells in pulmonary sarcoidosis and L\u00f6fgren's syndrome: friend or foe?","volume":"87","author":"Miedema","year":"2018","journal-title":"J Autoimmun"},{"key":"2023032109030146500_","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1146\/annurev-immunol-030409-101212","article-title":"Differentiation of effector CD4 T cell populations (*)","volume":"28","author":"Zhu","year":"2010","journal-title":"Annu Rev Immunol"},{"key":"2023032109030146500_","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1038\/s41467-019-09913-4","article-title":"Lipopolysaccharide inhalation recruits monocytes and dendritic cell subsets to the alveolar airspace","volume":"10","author":"Jardine","year":"2019","journal-title":"Nat Commun"},{"key":"2023032109030146500_","doi-asserted-by":"crossref","first-page":"2702","DOI":"10.3389\/fimmu.2019.02702","article-title":"Long-term exposure to inflammation induces differential cytokine patterns and apoptosis in dendritic cells","volume":"10","author":"Carstensen","year":"2019","journal-title":"Front Immunol"},{"key":"2023032109030146500_","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.immuni.2014.08.006","article-title":"Human dermal CD14\u207a cells are a transient population of monocyte-derived macrophages","volume":"41","author":"McGovern","year":"2014","journal-title":"Immunity"},{"key":"2023032109030146500_","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1016\/j.immuni.2013.04.011","article-title":"IRF4 transcription factor-dependent CD11b+ dendritic cells in human and mouse control mucosal IL-17 cytokine responses","volume":"38","author":"Schlitzer","year":"2013","journal-title":"Immunity"},{"key":"2023032109030146500_","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/j.immuni.2012.10.018","article-title":"Human inflammatory dendritic cells induce Th17 cell differentiation","volume":"38","author":"Segura","year":"2013","journal-title":"Immunity"},{"key":"2023032109030146500_","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/jid.2008.194","article-title":"Psoriasis is characterized by accumulation of immunostimulatory and Th1\/Th17 cell-polarizing myeloid dendritic cells","volume":"129","author":"Zaba","year":"2009","journal-title":"J Investig Dermatol"},{"key":"2023032109030146500_","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1097\/MCP.0000000000000403","article-title":"Transcriptome profiles in sarcoidosis and their potential role in disease prediction","volume":"23","author":"Schupp","year":"2017","journal-title":"Curr Opin Pulm Med"}],"container-title":["Journal of Leukocyte Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/JLB.5A0321-162R","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/JLB.5A0321-162R","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/111\/4\/857\/49468204\/jlb11007.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/111\/4\/857\/49468204\/jlb11007.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T21:13:32Z","timestamp":1699391612000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jleukbio\/article\/111\/4\/857\/6885108"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,25]]},"references-count":34,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,8,25]]},"published-print":{"date-parts":[[2022,3,25]]}},"URL":"https:\/\/doi.org\/10.1002\/jlb.5a0321-162r","relation":{},"ISSN":["0741-5400","1938-3673"],"issn-type":[{"value":"0741-5400","type":"print"},{"value":"1938-3673","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,4]]},"published":{"date-parts":[[2021,8,25]]},"assertion":[{"value":"2021-08-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}