{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Arterbery AS"],"funding":["NCATS NIH HHS","NIDDK NIH HHS","NCI NIH HHS"],"pagination":["4040-51"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4874532"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["196(10)"],"pubmed_abstract":["A subset of human regulatory T cells (Tregs) can secrete IFN-γ or IL-17, and thus share features of TH1 or TH17 effector cells and lose suppressive function. The main factors driving this differentiation of Tregs toward a proinflammatory phenotype include IL-12 for TH1-like and IL-6 for TH17-type Tregs. In this study we show that Tregs of patients with de novo autoimmune hepatitis (dAIH) display increased frequencies of proinflammatory IFN-γ and IL-17 cytokines. Irrespective of a fully demethylated FOXP3 locus, Tregs of subjects with dAIH are functionally impaired. In line with the observed Treg phenotype, we detected the presence of two dominant cytokines (IL-12 and IL-6) clustering with CD68(+) monocyte/macrophage cells in livers of subjects with dAIH, and isolated monocytes of subjects with dAIH secrete high levels of proinflammatory IL-12 and IL-6, suggesting that this inflammatory milieu is key for functional impairment of Tregs. Importantly, the blockade of IFN-γ partially restores suppressive function of Tregs of subjects with dAIH, indicating that monocyte/macrophage-derived triggers might play a central role in Treg dysfunction and pathogenesis of dAIH."],"journal":["Journal of immunology (Baltimore, Md. : 1950)"],"pubmed_title":["Production of Proinflammatory Cytokines by Monocytes in Liver-Transplanted Recipients with De Novo Autoimmune Hepatitis Is Enhanced and Induces TH1-like Regulatory T Cells."],"pmcid":["PMC4874532"],"funding_grant_id":["UL1 TR000142","P30 DK034989","UL1 TR001863","P30 CA016359"],"pubmed_authors":["Arterbery AS","Lobritto SJ","Martinez M","Kleinewietfeld M","Avitzur Y","Osafo-Addo A","Hafler DA","Ciarleglio M","Ekong UD","Deng Y"],"additional_accession":[]},"is_claimable":false,"name":"Production of Proinflammatory Cytokines by Monocytes in Liver-Transplanted Recipients with De Novo Autoimmune Hepatitis Is Enhanced and Induces TH1-like Regulatory T Cells.","description":"A subset of human regulatory T cells (Tregs) can secrete IFN-γ or IL-17, and thus share features of TH1 or TH17 effector cells and lose suppressive function. The main factors driving this differentiation of Tregs toward a proinflammatory phenotype include IL-12 for TH1-like and IL-6 for TH17-type Tregs. In this study we show that Tregs of patients with de novo autoimmune hepatitis (dAIH) display increased frequencies of proinflammatory IFN-γ and IL-17 cytokines. Irrespective of a fully demethylated FOXP3 locus, Tregs of subjects with dAIH are functionally impaired. In line with the observed Treg phenotype, we detected the presence of two dominant cytokines (IL-12 and IL-6) clustering with CD68(+) monocyte/macrophage cells in livers of subjects with dAIH, and isolated monocytes of subjects with dAIH secrete high levels of proinflammatory IL-12 and IL-6, suggesting that this inflammatory milieu is key for functional impairment of Tregs. Importantly, the blockade of IFN-γ partially restores suppressive function of Tregs of subjects with dAIH, indicating that monocyte/macrophage-derived triggers might play a central role in Treg dysfunction and pathogenesis of dAIH.","dates":{"release":"2016-01-01T00:00:00Z","publication":"2016 May","modification":"2024-12-03T22:38:58.353Z","creation":"2019-03-27T02:14:11Z"},"accession":"S-EPMC4874532","cross_references":{"pubmed":["27183637"],"doi":["10.4049/jimmunol.1502276"]}}