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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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