{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lim CX"],"funding":["Austrian Science Fund FWF","LEO Foundation","Vienna Science and Technology Fund","Ann Theodore Foundation","Austrian Society of Pneumology"],"pagination":["1152-1164"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7617514"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["209(9)"],"pubmed_abstract":["<b>Rationale:</b> Chronic sarcoidosis is a complex granulomatous disease with limited treatment options that can progress over time. Understanding the molecular pathways contributing to disease would aid in new therapeutic development. <b>Objectives:</b> 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. <b>Methods:</b> Macrophages were cultivated <i>in vitro</i> from isolated peripheral blood CD14<sup>+</sup> 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 <i>Tsc2</i>-specific sarcoidosis mouse model were analyzed for validatory experiments. <b>Measurements and Main Results:</b> Monocyte-derived macrophages from patients with chronic sarcoidosis spontaneously formed extensive granulomas <i>in vitro</i> compared with healthy control participants. Transcriptomic analyses separated healthy and sarcoidosis macrophages and identified an enrichment in lipid metabolic processes. <i>In vitro</i> 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 <i>in vitro</i> and <i>in vivo</i> in a sarcoidosis mouse model. <b>Conclusions:</b> 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."],"journal":["American journal of respiratory and critical care medicine"],"pubmed_title":["Aberrant Lipid Metabolism in Macrophages Is Associated with Granuloma Formation in Sarcoidosis."],"pmcid":["PMC7617514"],"funding_grant_id":["P34023-B","P34266-B","2022","P36555","F 8308","P30972","LF-OC-21-000806","P30857-B28","LS18-058","P 34023","F 83","P 34266","P 30972","P 36555","P 30857"],"pubmed_authors":["El Jammal T","Mazic M","Pandey RV","Pacheco Y","Kleissl L","Weichhart T","Mayerhofer C","Stary G","Lim CX","Hengstschlager M","Bock C","Gonzales K","Sukhbaatar N","Redl A","Calender A","Krausgruber T"],"additional_accession":[]},"is_claimable":false,"name":"Aberrant Lipid Metabolism in Macrophages Is Associated with Granuloma Formation in Sarcoidosis.","description":"<b>Rationale:</b> Chronic sarcoidosis is a complex granulomatous disease with limited treatment options that can progress over time. Understanding the molecular pathways contributing to disease would aid in new therapeutic development. <b>Objectives:</b> 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. <b>Methods:</b> Macrophages were cultivated <i>in vitro</i> from isolated peripheral blood CD14<sup>+</sup> 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 <i>Tsc2</i>-specific sarcoidosis mouse model were analyzed for validatory experiments. <b>Measurements and Main Results:</b> Monocyte-derived macrophages from patients with chronic sarcoidosis spontaneously formed extensive granulomas <i>in vitro</i> compared with healthy control participants. Transcriptomic analyses separated healthy and sarcoidosis macrophages and identified an enrichment in lipid metabolic processes. <i>In vitro</i> 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 <i>in vitro</i> and <i>in vivo</i> in a sarcoidosis mouse model. <b>Conclusions:</b> 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.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 May","modification":"2026-04-08T19:52:54.049Z","creation":"2026-04-08T14:31:19.187Z"},"accession":"S-EPMC7617514","cross_references":{"pubmed":["38353578"],"doi":["10.1164/rccm.202307-1273OC"]}}