Histone deacetylase 1 controls CD4+ T cell trafficking in autoinflammatory diseases. Issue 119 (May 2021)

• Record Type: Journal Article
• Authors: Hamminger, Patricia; Marchetti, Luca; Preglej, Teresa; Platzer, René; Zhu, Ci; Kamnev, Anton; Rica, Ramona; Stolz, Valentina; Sandner, Lisa; Alteneder, Marlis; Kaba, Elisa; Waltenberger, Darina; Huppa, Johannes B.; Trauner, Michael; Bock, Christoph; Lyck, Ruth; Bauer, Jan; Dupré, Loïc; Seiser, Christian; Boucheron, Nicole; Engelhardt, Britta; Ellmeier, Wilfried
• Is Part Of: Journal of autoimmunity. Issue 119(2021)
• Publication Date: 2021-05
• Subjects: Histone deacetylases -- Experimental autoimmune encephalomyelitis -- Adoptive CD4+ T cell transfer colitis -- T cell migration; Autoimmunity -- Periodicals; Autoimmune diseases -- Periodicals; Autoantibodies -- Periodicals; Autoimmune Diseases -- Periodicals; Auto-immunité -- Périodiques; Maladies auto-immunes -- Périodiques; Electronic journals; 616.978005
• DOI: 10.1016/j.jaut.2021.102610
• Languages: English
• ISSNs: 0896-8411

Abstract

Abstract: 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. Graphical abstract: Image 1 Highlights: HDAC1 regulates CD4 + T cell adhesion to brain endothelial cells. Defects in CD4 + T cell migration underlie EAE protection of HDAC1 cKO mice. HDAC1 regulates homing of CD4 + T cells to intestinal tissues. CD4 + T cell-mediated induction of intestinal inflammation is controlled by HDAC1. HDAC1 controls CD4 + T cell-mediated autoimmunity via regulating T cell trafficking.