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

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.

• Authors: Patricia Hamminger, Luca Marchetti, Teresa Preglej, René Platzer, Ci Zhu, Anton Kamnev, Ramona Rica, Valentina Stolz, Lisa Sandner, Marlis Alteneder, Elisa Kaba, Darina Waltenberger, Johannes B Huppa, Michael Trauner, Christoph Bock, Ruth Lyck, Jan Bauer, Loïc Dupré, Christian Seiser, Nicole Boucheron, Britta Engelhardt, Wilfried Ellmeier
• Journal: Journal of autoimmunity (J Autoimmun) Vol. 119 Pg. 102610 (05 2021) ISSN: 1095-9157 [Electronic] England
• PMID: 33621930 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chemical References

• Biomarkers
• HDAC1 protein, human
• Histone Deacetylase 1

Topics

• Animals
• Autoimmunity
• Biomarkers
• CD4-Positive T-Lymphocytes (immunology, metabolism)
• Cell Adhesion
• Chemotaxis, Leukocyte (genetics, immunology)
• Disease Models, Animal
• Disease Susceptibility
• Encephalomyelitis, Autoimmune, Experimental (diagnosis, etiology, metabolism)
• Endothelial Cells
• Gene Expression Profiling
• Gene Expression Regulation
• Histone Deacetylase 1 (genetics, metabolism)
• Immunohistochemistry
• Inflammation (diagnosis, etiology, metabolism)
• Intestinal Mucosa (immunology, metabolism, pathology)
• Lymphocyte Activation (genetics, immunology)
• Mice
• Mice, Knockout