Journal
JOURNAL OF AUTOIMMUNITY
Volume 119, Issue -, Pages -Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jaut.2021.102610
Keywords
Histone deacetylases; Experimental autoimmune encephalomyelitis; Adoptive CD4(+) T cell transfer colitis; T cell migration
Categories
Funding
- Austrian Science Fund (FWF) [P19930, P23641, P26193, P29790]
- Medical University of Vienna doctoral programs [DK W1212]
- Boehringer Ingelheim Fonds
- Vienna Science and Technology Fund [WWTF-LS16-060, WWTF-LS14-031]
- DOC fellowship of the Austrian Academy of Sciences
- Swiss National Science Foundation [SNSF 31003A_170131]
- European Union [675619-BtRAIN]
- (DOC 32 doc.fund) TissueHome
- Austrian Science Fund (FWF) [P26193, P23641, P19930, P29790] Funding Source: Austrian Science Fund (FWF)
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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.
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.
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