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Understanding the molecular pathways contributing to disease would aid in new therapeutic development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To understand whether macrophages from patients with nonresolving chronic sarcoidosis are predisposed to macrophage aggregation and granuloma formation and whether modulation of the underlying molecular pathways influence sarcoidosis granuloma formation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Macrophages were cultivated in vitro from isolated peripheral blood CD14+ monocytes and evaluated for spontaneous aggregation. Transcriptomics analyses and phenotypic and drug inhibitory experiments were performed on these monocyte-derived macrophages. Human skin biopsies from patients with sarcoidosis and a myeloid Tsc2-specific sarcoidosis mouse model were analyzed for validatory experiments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Monocyte-derived macrophages from patients with chronic sarcoidosis spontaneously formed extensive granulomas in vitro compared with healthy control participants. Transcriptomic analyses separated healthy and sarcoidosis macrophages and identified an enrichment in lipid metabolic processes. In vitro patient granulomas, sarcoidosis mouse model granulomas, and those directly analyzed from lesional patient skin expressed an aberrant lipid metabolism profile and contained increased neutral lipids. Conversely, a combination of statins and cholesterol-reducing agents reduced granuloma formation both in vitro and in vivo in a sarcoidosis mouse model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Together, our findings show that altered lipid metabolism in sarcoidosis macrophages is associated with its predisposition to granuloma formation and suggest cholesterol-reducing therapies as a treatment option in patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202307-1273oc","type":"journal-article","created":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T09:14:36Z","timestamp":1707902076000},"page":"1152-1164","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":26,"title":["Aberrant Lipid Metabolism in Macrophages Is Associated with Granuloma Formation in Sarcoidosis"],"prefix":"10.1093","volume":"209","author":[{"given":"Clarice X.","family":"Lim","sequence":"first","affiliation":[{"name":"Institute of Medical Genetics, Center of Pathobiochemistry and Genetics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Redl","sequence":"additional","affiliation":[{"name":"Department of Dermatology, and"},{"name":"CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Kleissl","sequence":"additional","affiliation":[{"name":"Department of Dermatology, and"},{"name":"CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram Vinay","family":"Pandey","sequence":"additional","affiliation":[{"name":"Department of Dermatology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Mayerhofer","sequence":"additional","affiliation":[{"name":"Department of Dermatology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"El Jammal","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics, Center of Pathobiochemistry and Genetics"},{"name":"Laboratory of Tissue Biology and Therapeutic Engineering, CNRS UMR5305, University Claude Bernard Lyon 1, IBCP, Lyon, France; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Mazic","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics, Center of Pathobiochemistry and Genetics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karine","family":"Gonzales","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics, Center of Pathobiochemistry and Genetics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nyamdelger","family":"Sukhbaatar","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics, Center of Pathobiochemistry and Genetics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Krausgruber","sequence":"additional","affiliation":[{"name":"Institute of Artificial Intelligence, Center for Medical Data Science, Medical University of Vienna, Vienna, Austria"},{"name":"CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Bock","sequence":"additional","affiliation":[{"name":"Institute of Artificial Intelligence, Center for Medical Data Science, Medical University of Vienna, Vienna, Austria"},{"name":"CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Hengstschl\u00e4ger","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics, Center of Pathobiochemistry and Genetics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Calender","sequence":"additional","affiliation":[{"name":"Laboratory of Tissue Biology and Therapeutic Engineering, CNRS UMR5305, University Claude Bernard Lyon 1, IBCP, Lyon, France; 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