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

Hamminger, P.; Marchetti, L.; Preglej, T.; Platzer, R.; Zhu, C.; Kamnev, A.; Rica, R.; Stolz, V.; Sandner, L.; Alteneder, M.; Kaba, E.; Waltenberger, D.; Huppa, J.B.; Trauner, M.; Bock, C.; Lyck, R.; Bauer, J.; Dupré, L.; Seiser, C.; Boucheron, N.; Engelhardt, B.; Ellmeier, W.

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

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Item Type:	Article
Title:	Histone deacetylase 1 controls CD4(+) T cell trafficking in autoinflammatory diseases
Creators Name:	Hamminger, P., Marchetti, L., Preglej, T., Platzer, R., Zhu, C., Kamnev, A., Rica, R., Stolz, V., Sandner, L., Alteneder, M., Kaba, E., Waltenberger, D., Huppa, J.B., Trauner, M., Bock, C., Lyck, R., Bauer, J., Dupré, L., Seiser, C., Boucheron, N., Engelhardt, B. and Ellmeier, W.
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.
Keywords:	Histone Deacetylases, Experimental Autoimmune Encephalomyelitis, Adoptive CD4+ T Cell Transfer Colitis, T Cell Migration, Animals, Mice
Source:	Journal of Autoimmunity
ISSN:	0896-8411
Publisher:	Elsevier
Volume:	119
Page Range:	102610
Date:	May 2021
Official Publication:	https://doi.org/10.1016/j.jaut.2021.102610
PubMed:	View item in PubMed

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