{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T04:49:29Z","timestamp":1791002969115,"version":"4.1.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2019,1,1]],"date-time":"2019-01-01T00:00:00Z","timestamp":1546300800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The mechanisms underlying abnormal granuloma formation in patients with sarcoidosis are complex and remain poorly understood. A novel in vitro human granuloma model was used to determine the molecular mechanisms of granuloma genesis in patients with sarcoidosis in response to putative disease-causing mycobacterial antigens. Peripheral blood mononuclear cells (PBMCs) from patients with active sarcoidosis and from normal, disease-free control subjects were incubated for 7 days with purified protein derivative\u2013coated polystyrene beads. Molecular responses, as reflected by differential expression of genes, extracellular cytokine patterns, and cell surface receptor expression, were analyzed. Unbiased systems biology approaches were used to identify signaling pathways engaged during granuloma formation. Model findings were compared with human lung and mediastinal lymph node gene expression profiles. Compared with identically treated PBMCs of control subjects (n\u2009=\u20095), purified protein derivative\u2013treated sarcoidosis PBMCs (n\u2009=\u20096) were distinguished by the formation of cellular aggregates resembling granulomas. Ingenuity Pathway Analysis of differential expression gene patterns identified molecular pathways that are primarily regulated by IL-13, which promotes alternatively activated (M2) macrophage polarization. M2 polarization was further demonstrated by immunohistochemistry performed on the in vitro sarcoidosis granuloma-like structures. IL-13\u2013regulated gene pathways were confirmed in human sarcoidosis lung and mediastinal lymph node tissues. The in vitro human sarcoidosis granuloma model provides novel insights into early granuloma formation, particularly IL-13 regulation of molecular networks that regulate M2 macrophage polarization. M2 macrophages are predisposed to aggregation and multinucleated giant cell formation, which are characteristic features of sarcoidosis granulomas.<\/jats:p>\n                  <jats:p>Clinical trial registered with www.clinicaltrials.gov (NCT01857401).<\/jats:p>","DOI":"10.1165\/rcmb.2018-0053oc","type":"journal-article","created":{"date-parts":[[2018,8,22]],"date-time":"2018-08-22T18:27:40Z","timestamp":1534962460000},"page":"84-95","source":"Crossref","is-referenced-by-count":77,"title":["IL-13\u2013regulated Macrophage Polarization during Granuloma Formation in an\n                    <i>In Vitro<\/i>\n                    Human Sarcoidosis Model"],"prefix":"10.1093","volume":"60","author":[{"given":"Landon W.","family":"Locke","sequence":"first","affiliation":[{"name":"Department of Microbial Infection and Immunity, Center for Microbial Interface Biology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3197-6746","authenticated-orcid":false,"given":"Elliott D.","family":"Crouser","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care, and Sleep Medicine, The Dorothy M. Davis Heart and Lung Research Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"White","sequence":"additional","affiliation":[{"name":"The Institute for Genomic Medicine, Nationwide Children\u2019s Hospital, Columbus, Ohio; and"},{"name":"Department of Pediatrics, College of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark W.","family":"Julian","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care, and Sleep Medicine, The Dorothy M. Davis Heart and Lung Research Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyn Guirado","family":"Caceres","sequence":"additional","affiliation":[{"name":"Department of Microbial Infection and Immunity, Center for Microbial Interface Biology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey C.","family":"Papp","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology and Genetics, The Ohio State University Wexner Medical Center, Columbus, Ohio; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Van T.","family":"Le","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care, and Sleep Medicine, The Dorothy M. 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