Critical Role of Histone Demethylase Jmjd3 in T Cell Migration

Jmjd3, a histone H3K27 demethylase, is known to play a critical role in macrophage and T cell differentiation, but its role in T cell migration and T cell memory maintenance remains largely unknown. In this study, we show that Jmjd3 deficiency resulted in multiple alterations in T cell migration. Jmjd3 deletion limits CD4⁺ T cells egress out of the thymus, leading to thymic T-cell accumulation and peripheral lymphoid organ T-cell reduction. Gene profiling analysis of wild-type and Jmjd3-deficient CD4⁺ T cells identified altered expression of Jmjd3 target genes that correlated with changes in H3K27 and/or H3K4 trimethylation in promoters and gene body regions. The expression of the Jmjd3 target gene Pdlim4 is also regulated by Klf2, which regulates T-cell migration. Thus, our findings identify a novel Jmjd3 target gene, Pdlim4, in CD4⁺ T cell migration and provide insight into the molecular mechanisms by which Jmjd3 regulates T-cell migration.