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

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; ... (2021). Histone deacetylase 1 controls CD4+ T cell trafficking in autoinflammatory diseases. Journal of autoimmunity, 119, p. 102610. Elsevier 10.1016/j.jaut.2021.102610

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

UniBE Contributor:

Marchetti, Luca; Kaba, Elisa; Lyck, Ruth and Engelhardt, Britta

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0896-8411

Publisher:

Elsevier

Language:

English

Submitter:

Cindy Carolyn Alpinice Schumacher

Date Deposited:

21 Dec 2021 11:40

Last Modified:

26 Dec 2021 01:49

Publisher DOI:

10.1016/j.jaut.2021.102610

PubMed ID:

33621930

Uncontrolled Keywords:

Adoptive CD4(+) T cell transfer colitis Experimental autoimmune encephalomyelitis Histone deacetylases T cell migration

BORIS DOI:

10.48350/162863

URI:

https://boris.unibe.ch/id/eprint/162863

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