Histone deacetylase 1 controls CD4+ T cell trafficking in autoinflammatory diseases

CD4(+) T cell trafficking is a fundamental property of adaptive immunity. In this study, we uncover a novel role for histone deacetylase 1 (HDAC1) in controlling effector CD4(+) T cell migration, thereby providing mechanistic insight into why a T cell-specific deletion of HDAC1 protects against experimental autoimmune encephalomyelitis (EAE). HDAC1-deficient CD4(+) T cells downregulated genes associated with leukocyte extravasation. In vitro, HDAC1-deficient CD4(+) T cells displayed aberrant morphology and migration on surfaces coated with integrin LFA-1 ligand ICAM-1 and showed an impaired ability to arrest on and to migrate across a monolayer of primary mouse brain microvascular endothelial cells under physiological flow. Moreover, HDAC1 deficiency reduced homing of CD4(+) T cells into the intestinal epithelium and lamina propria preventing weight-loss, crypt damage and intestinal inflammation in adoptive CD4(+) T cell transfer colitis. This correlated with reduced expression levels of LFA-1 integrin chains CD11a and CD18 as well as of selectin ligands CD43, CD44 and CD162 on transferred circulating HDAC1-deficient CD4(+) T cells. Our data reveal that HDAC1 controls T cell-mediated autoimmunity via the regulation of CD4(+) T cell trafficking into the CNS and intestinal tissues.

Automated summary

This study reveals the significant role of histone deacetylase 1 (HDAC1) in controlling effector CD4(+) T cell migration, preventing experimental autoimmune encephalomyelitis. HDAC1-deficient CD4(+) T cells exhibit abnormal migration and morphology on surfaces coated with integrin LFA-1 ligand ICAM-1.