{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:02:46Z","timestamp":1792785766104,"version":"4.5.0"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003390","name":"Fritz Thyssen Foundation","doi-asserted-by":"publisher","award":["10.21.2.021MN"],"award-info":[{"award-number":["10.21.2.021MN"]}],"id":[{"id":"10.13039\/501100003390","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Else Kr\u00f6ner-Fresenius Foundation","award":["2023_EKCS.18"],"award-info":[{"award-number":["2023_EKCS.18"]}]},{"name":"Ann Theodore Foundation"},{"DOI":"10.13039\/501100010564","name":"German Center for Lung Research","doi-asserted-by":"publisher","award":["FKZ 82DZL002B1"],"award-info":[{"award-number":["FKZ 82DZL002B1"]}],"id":[{"id":"10.13039\/501100010564","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010564","name":"German Center for Lung Research","doi-asserted-by":"publisher","award":["FKZ 82DZL002C1"],"award-info":[{"award-number":["FKZ 82DZL002C1"]}],"id":[{"id":"10.13039\/501100010564","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010564","name":"German Center for Lung Research","doi-asserted-by":"publisher","award":["FKZ 82DZLT82C1"],"award-info":[{"award-number":["FKZ 82DZLT82C1"]}],"id":[{"id":"10.13039\/501100010564","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sarcoidosis is a disease of unknown etiology, characterized by the formation of immune cell accumulations (granulomas) in the lung and other tissues. Chronic sarcoidosis may lead to pulmonary fibrosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To unravel cellular niches within pulmonary granulomas of patients with chronic sarcoidosis using spatial transcriptomics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Spatial transcriptomics using the Visium platform (10x Genomics) was performed on 9 granuloma-containing lung explants from patients with sarcoidosis. Validation of gene expression was performed through immunohistofluorescence protein staining and RNA in situ hybridization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Spatial gene expression covered 30,587 gene expression spots and 173 granulomas. A CD68+\u2009macrophage niche was localized in the center of the granuloma, with a CD3+\u2009T-cell and CD20+\u2009B-cell niche in close proximity, surrounded by a COL3A1+\u2009fibroblast niche. In the Central Granuloma Macrophage niche, expression of the profibrotic macrophage genes SPP1, CHIT1, and CHI3L1 was observed, genes whose expression has recently been described for macrophages in idiopathic pulmonary fibrosis. Additionally, proinflammatory macrophage genes were expressed in the Central Granuloma Macrophage niche, suggesting that macrophages were armed for lysosomal degradation and ready for phagocytosis. Inner granuloma niches showed higher expression of interferon gamma (IFN-\u03b3)\u2013inducible genes. Higher collagen and CTHRC1 expression were observed in fibroblast-containing granuloma niches, characteristics of profibrotic lung remodeling. Ligand-receptor analysis identified proinflammatory and profibrotic interactions between granuloma niches.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Taken together, macrophages in the center of the sarcoidosis granuloma form an armed-and-ready, hybrid proinflammatory and profibrotic niche, supporting granuloma persistence through continuous IFN-\u03b3 stimulation and collagen expression by fibroblasts localized in the periphery of the granuloma.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ajrccm\/aamaf089","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T12:20:15Z","timestamp":1767615615000},"page":"338-350","source":"Crossref","is-referenced-by-count":4,"title":["Spatial transcriptomics uncovers hybrid, proinflammatory, and profibrotic cellular niches in pulmonary granuloma of patients with chronic sarcoidosis"],"prefix":"10.1093","volume":"212","author":[{"given":"Leonard","family":"Christian","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine and Infectious Diseases, Hannover Medical School (MHH) , Hannover,","place":["Germany"]},{"name":"Biomedical Research in End-Stage and Obstructive Lung Disease (BREATH), Hannover Medical School (MHH), German Center for Lung Research (DZL) , Hannover,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hande","family":"Yilmaz","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine and Infectious Diseases, Hannover Medical School (MHH) , Hannover,","place":["Germany"]},{"name":"Biomedical Research in End-Stage and Obstructive Lung Disease (BREATH), Hannover Medical School (MHH), German Center for Lung Research (DZL) , Hannover,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jannik","family":"Ruwisch","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine and Infectious Diseases, Hannover Medical School (MHH) , Hannover,","place":["Germany"]},{"name":"Biomedical Research in End-Stage and Obstructive Lung Disease (BREATH), Hannover Medical School (MHH), German Center for Lung Research (DZL) , Hannover,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon","family":"Giercke","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine and Infectious Diseases, Hannover Medical School (MHH) , Hannover,","place":["Germany"]},{"name":"Biomedical Research in End-Stage and Obstructive Lung Disease (BREATH), Hannover Medical School (MHH), German Center for Lung Research (DZL) , 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