JMJD3 regulates CD4 T cell trafficking by targeting actin cytoskeleton regulatory gene Pdlim4.

ABSTRACT: Histone H3K27 demethylase, JMJD3 plays a critical role in gene expression and T-cell differentiation. However, the role and mechanisms of JMJD3 in T cell trafficking remain poorly understood. Here we show that JMJD3 deficiency in CD4+ T cells resulted in an accumulation of T cells in the thymus, and reduction of T cell number in the secondary lymphoid organs. We identified PDLIM4 as a significantly down-regulated target gene in JMJD3-deficient CD4+ T cells by gene profiling and ChIP-seq analyses. We further showed that PDLIM4 functioned as an adaptor protein to interact with S1P1 and filamentous actin (F-actin), thus serving as a key regulator of T cell trafficking. Mechanistically, JMJD3 bound to the promoter and gene body regions of Pdlim4 gene and regulated its expression by interacting

SUBMITTER: Fu C 

PROVIDER: S-EPMC6819100 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature