{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Bibby JA"],"funding":["Intramural Research Programs of the National Human Genome Research Institute","Innovative Medicines Initiative","Medical Research Council","National Institute for Health Research (NIHR)","RCUK | Medical Research Council","Wellcome Trust"],"pagination":["3412"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7343868"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["11(1)"],"pubmed_abstract":["Regulatory B cells restrict immune and inflammatory responses across a number of contexts. This capacity is mediated primarily through the production of IL-10. Here we demonstrate that the induction of a regulatory program in human B cells is dependent on a metabolic priming event driven by cholesterol metabolism. Synthesis of the metabolic intermediate geranylgeranyl pyrophosphate (GGPP) is required to specifically drive IL-10 production, and to attenuate Th1 responses. Furthermore, GGPP-dependent protein modifications control signaling through PI3Kδ-AKT-GSK3, which in turn promote BLIMP1-dependent IL-10 production. Inherited gene mutations in cholesterol metabolism result in a severe autoinflammatory syndrome termed mevalonate kinase deficiency (MKD). Consistent with our findings, B cell"],"journal":["Nature communications"],"pubmed_title":["Cholesterol metabolism drives regulatory B cell IL-10 through provision of geranylgeranyl pyrophosphate."],"pmcid":["PMC7343868"],"funding_grant_id":["206618/Z/17/Z","777357","115142-2","MR/M012328/2"],"pubmed_authors":["Rosenzweig S","Perucha E","Bibby JA","Okkenhaug K","Chandra A","Hayday T","Kemper C","Cope AP","Purvis HA","Lachmann HJ","Aksentijevich I","Wood M"],"additional_accession":[]},"is_claimable":false,"name":"Cholesterol metabolism drives regulatory B cell IL-10 through provision of geranylgeranyl pyrophosphate.","description":"Regulatory B cells restrict immune and inflammatory responses across a number of contexts. This capacity is mediated primarily through the production of IL-10. Here we demonstrate that the induction of a regulatory program in human B cells is dependent on a metabolic priming event driven by cholesterol metabolism. Synthesis of the metabolic intermediate geranylgeranyl pyrophosphate (GGPP) is required to specifically drive IL-10 production, and to attenuate Th1 responses. Furthermore, GGPP-dependent protein modifications control signaling through PI3Kδ-AKT-GSK3, which in turn promote BLIMP1-dependent IL-10 production. Inherited gene mutations in cholesterol metabolism result in a severe autoinflammatory syndrome termed mevalonate kinase deficiency (MKD). Consistent with our findings, B cell","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Jul","modification":"2025-04-22T19:34:37.595Z","creation":"2025-04-06T02:47:32.855Z"},"accession":"S-EPMC7343868","cross_references":{"pubmed":["32641742"],"doi":["10.1038/s41467-020-17179-4"]}}