{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Savage TM"],"funding":["NIDDK NIH HHS","NIAID NIH HHS","NHLBI NIH HHS","NCI NIH HHS","NIGMS NIH HHS"],"pagination":["303-318.e6"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10922825"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["57(2)"],"pubmed_abstract":["Production of amphiregulin (Areg) by regulatory T (Treg) cells promotes repair after acute tissue injury. Here, we examined the function of Treg cells in non-alcoholic steatohepatitis (NASH), a setting of chronic liver injury. Areg-producing Treg cells were enriched in the livers of mice and humans with NASH. Deletion of Areg in Treg cells, but not in myeloid cells, reduced NASH-induced liver fibrosis. Chronic liver damage induced transcriptional changes associated with Treg cell activation. Mechanistically, Treg cell-derived Areg activated pro-fibrotic transcriptional programs in hepatic stellate cells via epidermal growth factor receptor (EGFR) signaling. Deletion of Areg in Treg cells protected mice from NASH-dependent glucose intolerance, which also was dependent on EGFR signaling on hepatic stellate cells. Areg from Treg cells promoted hepatocyte gluconeogenesis through hepatocyte detection of hepatic stellate cell-derived interleukin-6. Our findings reveal a maladaptive role for Treg cell-mediated tissue repair functions in chronic liver disease and link liver damage to NASH-dependent glucose intolerance."],"journal":["Immunity"],"pubmed_title":["Amphiregulin from regulatory T cells promotes liver fibrosis and insulin resistance in non-alcoholic steatohepatitis."],"pmcid":["PMC10922825"],"funding_grant_id":["K22 AI127847","R01 DK128955","T32 GM007367","P30 DK132710","R01 HL148718","R01 DK135298","P30 CA013696"],"pubmed_authors":["Adam J","Savage TM","Fortson KT","Rouanne M","Li F","Haeusler RA","Shayya H","Schwabe RF","Gamarra JR","Arpaia N","de Los Santos-Alexis K","Han A","Oliveras-Alsina A","Cavero R","Rae SS","Kornberg A"],"additional_accession":[]},"is_claimable":false,"name":"Amphiregulin from regulatory T cells promotes liver fibrosis and insulin resistance in non-alcoholic steatohepatitis.","description":"Production of amphiregulin (Areg) by regulatory T (Treg) cells promotes repair after acute tissue injury. Here, we examined the function of Treg cells in non-alcoholic steatohepatitis (NASH), a setting of chronic liver injury. Areg-producing Treg cells were enriched in the livers of mice and humans with NASH. Deletion of Areg in Treg cells, but not in myeloid cells, reduced NASH-induced liver fibrosis. Chronic liver damage induced transcriptional changes associated with Treg cell activation. Mechanistically, Treg cell-derived Areg activated pro-fibrotic transcriptional programs in hepatic stellate cells via epidermal growth factor receptor (EGFR) signaling. Deletion of Areg in Treg cells protected mice from NASH-dependent glucose intolerance, which also was dependent on EGFR signaling on hepatic stellate cells. Areg from Treg cells promoted hepatocyte gluconeogenesis through hepatocyte detection of hepatic stellate cell-derived interleukin-6. Our findings reveal a maladaptive role for Treg cell-mediated tissue repair functions in chronic liver disease and link liver damage to NASH-dependent glucose intolerance.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Feb","modification":"2026-06-01T17:50:51.436Z","creation":"2025-04-04T01:12:18.874Z"},"accession":"S-EPMC10922825","cross_references":{"pubmed":["38309273"],"doi":["10.1016/j.immuni.2024.01.009"]}}