Conditional Deletion of Histone Deacetylase 1 in T Cells Leads to Enhanced Airway Inflammation and Increased Th2 Cytokine Production
| Autor: | Gordin Zupkovitz, Ivan Bilic, Patrick Matthias, Lamia El-Housseiny, Martin Gaisberger, Roland Tschismarov, Martina Rembold, Yu Zhang, Arnulf Hartl, Nicole Boucheron, Christian Seiser, Reinhard Grausenburger, Michelle M. Epstein, Wilfried Ellmeier |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
T cell
Immunology T lymphocytes development Histone Deacetylase 1 Mice Transgenic Biology Article CCL5 TCIRG1 Mice Interleukin 21 Th2 Cells Respiratory Hypersensitivity medicine Animals Immunology and Allergy Cytotoxic T cell IL-2 receptor Lung Cells Cultured Interleukin 3 Inflammation ZAP70 Cell Polarity Th1 Cells Up-Regulation Cell biology Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Cytokines |
| Zdroj: | The Journal of Immunology. 185:3489-3497 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Chromatin modifications, such as reversible histone acetylation, play a key role in the regulation of T cell development and function. However, the role of individual histone deacetylases (HDACs) in T cells is less well understood. In this article, we show by conditional gene targeting that T cell-specific loss of HDAC1 led to an increased inflammatory response in an in vivo allergic airway inflammation model. Mice with HDAC1-deficient T cells displayed an increase in all critical parameters in this Th2-type asthma model, such as eosinophil recruitment into the lung, mucus hypersecretion, parenchymal lung inflammation, and enhanced airway resistance. This correlated with enhanced Th2 cytokine production in HDAC1-deficient T cells isolated from diseased mice. In vitro-polarized HDAC1-deficient Th2 cells showed a similar enhancement of IL-4 expression, which was evident already at day 3 of Th2 differentiation cultures and restricted to T cell subsets that underwent several rounds of cell divisions. HDAC1 was recruited to the Il4 gene locus in ex vivo isolated nonstimulated CD4+ T cells, indicating a direct control of the Il4 gene locus. Our data provide genetic evidence that HDAC1 is an essential HDAC that controls the magnitude of an inflammatory response by modulating cytokine expression in effector T cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|