A Stk4-Foxp3-NF-κB p65 transcriptional complex promotes T_reg cell activation and homeostasis.

ABSTRACT: The 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-κB 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 T_reg cell p65 expression and nuclear translocation, impaired NF-κB p65-Foxp3 complex formation, and defective

SUBMITTER: Cui Y 

PROVIDER: S-EPMC9816918 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature