Hamminger, PatriciaPatriciaHammingerMarchetti, LucaLucaMarchettiPreglej, TeresaTeresaPreglejPlatzer, RenéRenéPlatzerZhu, CiCiZhuKamnev, AntonAntonKamnevRica, RamonaRamonaRicaStolz, ValentinaValentinaStolzSandner, LisaLisaSandnerAlteneder, MarlisMarlisAltenederBouillet, Elisa CatherineElisa CatherineBouilletWaltenberger, DarinaDarinaWaltenbergerHuppa, Johannes BJohannes BHuppaTrauner, MichaelMichaelTraunerBock, ChristophChristophBockLyck, RuthRuthLyck0000-0002-6479-4837Bauer, JanJanBauerDupré, LoïcLoïcDupréSeiser, ChristianChristianSeiserBoucheron, NicoleNicoleBoucheronEngelhardt, BrittaBrittaEngelhardt0000-0003-3059-9846Ellmeier, WilfriedWilfriedEllmeier2024-10-062024-10-062021-05https://boris-portal.unibe.ch/handle/20.500.12422/58756CD4+ 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.enAdoptive CD4(+) T cell transfer colitis Experimental autoimmune encephalomyelitis Histone deacetylases T cell migration600 - Technology::610 - Medicine & healtharticle10.48350/1628633362193010.1016/j.jaut.2021.102610