A Stk4-Foxp3-NF-?B p65 transcriptional complex promotes Treg cell activation and homeostasis

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dc.contributor.authorCui, Ye
dc.contributor.authorBenamar, Mehdi
dc.contributor.authorSchmitz-Abe, Klaus
dc.contributor.authorPoondi-Krishnan, Varsha
dc.contributor.authorChen, Qian
dc.contributor.authorJugder, Bat-Erdene
dc.contributor.authorFatou, Benoit
dc.date.accessioned2024-02-23T14:26:09Z
dc.date.available2024-02-23T14:26:09Z
dc.date.issued2022
dc.departmentNEÜen_US
dc.description.abstractThe molecular programs involved in regulatory T (T-reg) cell activation and homeostasis remain incompletely understood. Here, we show that T cell receptor (TCR) signaling in T-reg cells induces the nuclear translocation of serine/threonine kinase 4 (Stk4), leading to the formation of an Stk4-NF-kappa B p65-Foxp3 complex that regulates Foxp3- and p65-dependent transcriptional programs. This complex was stabilized by Stk4-dependent phosphorylation of Foxp3 on serine-418. Stk4 deficiency in T-reg cells, either alone or in combination with its homolog Stk3, precipitated a fatal autoimmune lymphoproliferative disease in mice characterized by decreased Treg cell p65 expression and nuclear translocation, impaired NF-kappa B p65-Foxp3 complex formation, and defective Treg cell activation. In an adoptive immunotherapy model, overexpression of p65 or the phosphomimetic Foxp3S418E in Stk3/4-deficient T-reg cells ameliorated their immune regulatory defects. Our studies identify Stk4 as an essential TCR-responsive regulator of p65-Foxp3-dependent transcription that promotes T-reg cellmediated immune tolerance.en_US
dc.description.sponsorshipNIH [R01AI085090, R01AI128976, R01AI153174]en_US
dc.description.sponsorshipThis work was supported by NIH grants R01AI085090 and R01AI128976 to T.A.C. and grant R01AI153174 to L.-M.C.en_US
dc.identifier.doi10.1126/sciimmunol.abl8357
dc.identifier.issn2470-9468
dc.identifier.issue75en_US
dc.identifier.pmid36149942en_US
dc.identifier.scopus2-s2.0-85138458537en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.1126/sciimmunol.abl8357
dc.identifier.urihttps://hdl.handle.net/20.500.12452/14072
dc.identifier.volume7en_US
dc.identifier.wosWOS:000933998800005en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherAmer Assoc Advancement Scienceen_US
dc.relation.ispartofScience Immunologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subject[Keyword Not Available]en_US
dc.titleA Stk4-Foxp3-NF-?B p65 transcriptional complex promotes Treg cell activation and homeostasisen_US
dc.typeArticleen_US

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