The Crucial Roles of JMJD3 in T Cell Trafficking and Persistence

Abstract

Jmjd3, a histone H3K27 demethylase, regulates macrophage and T-cell differentiation, but its role in T-cell trafficking and persistence remains largely unknown. In this dissertation, I show that Jmjd3 deficiency in CD4^+ T cells limits CD4^+ T-cell egress out of the thymus, leading to thymic T-cell accumulation, and Jmjd3 deletion limits peripheral CD4^+ T-cell migration, leading to a reduced number of T cells in secondary lymphoid organs. Further investigation identified Pdlim4 as a novel Jmjd3 target gene that affects T-cell trafficking by cooperating with S1P1. Jmjd3 deficiency also enables T-cell persistence due to an increase in proliferation and a decrease in apoptosis, suggesting that the H3K27 demethylase Jmjd3 may be a good therapeutic target for adoptive immunotherapy for the generation of superior T cell grafts.