{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Xu H"],"funding":["Howard Hughes Medical Institute","National Institutes of Health","Cancer Research Institute","Helen and Martin Kimmel Center for Biology and Medicine"],"pagination":["e20210777"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8421263"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["218(11)"],"pubmed_abstract":["TGF-β signaling is fundamental for both Th17 and regulatory T (Treg) cell differentiation. However, these cells differ in requirements for downstream signaling components, such as SMAD effectors. To further characterize mechanisms that distinguish TGF-β signaling requirements for Th17 and Treg cell differentiation, we investigated the role of Arkadia (RNF111), an E3 ubiquitin ligase that mediates TGF-β signaling during development. Inactivation of Arkadia in CD4+ T cells resulted in impaired Treg cell differentiation in vitro and loss of RORγt+FOXP3+ iTreg cells in the intestinal lamina propria, which increased susceptibility to microbiota-induced mucosal inflammation. In contrast, Arkadia was dispensable for Th17 cell responses. Furthermore, genetic ablation of two Arkadia substrates, the"],"journal":["The Journal of experimental medicine"],"pubmed_title":["Arkadia-SKI/SnoN signaling differentially regulates TGF-β-induced iTreg and Th17 cell differentiation."],"pmcid":["PMC8421263"],"funding_grant_id":["2R01AI080885"],"pubmed_authors":["Raghavan V","Nguyen HH","Episkopou V","Littman DR","Wu L","Mesa KR","Xu H"],"additional_accession":[]},"is_claimable":false,"name":"Arkadia-SKI/SnoN signaling differentially regulates TGF-β-induced iTreg and Th17 cell differentiation.","description":"TGF-β signaling is fundamental for both Th17 and regulatory T (Treg) cell differentiation. However, these cells differ in requirements for downstream signaling components, such as SMAD effectors. To further characterize mechanisms that distinguish TGF-β signaling requirements for Th17 and Treg cell differentiation, we investigated the role of Arkadia (RNF111), an E3 ubiquitin ligase that mediates TGF-β signaling during development. Inactivation of Arkadia in CD4+ T cells resulted in impaired Treg cell differentiation in vitro and loss of RORγt+FOXP3+ iTreg cells in the intestinal lamina propria, which increased susceptibility to microbiota-induced mucosal inflammation. In contrast, Arkadia was dispensable for Th17 cell responses. Furthermore, genetic ablation of two Arkadia substrates, the","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Nov","modification":"2025-04-05T14:05:25.584Z","creation":"2025-04-05T14:05:25.584Z"},"accession":"S-EPMC8421263","cross_references":{"pubmed":["34473197"],"doi":["10.1084/jem.20210777"]}}