title: Conditional deletion of histone deacetylase 1 in T cells leads to enhanced airway inflammation and increased Th2 cytokine production.
abstract: 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.
authors: Department of Medical Biochecmistry, Max F. Perutz Laboratories, Vienna Biocenter, Vienna, Austria.
authors: Reinhard
authors: R
authors: Grausenburger
authors: Ivan
authors: I
authors: Bilic
authors: Nicole
authors: N
authors: Boucheron
authors: Gordin
authors: G
authors: Zupkovitz
authors: Lamia
authors: L
authors: El-Housseiny
authors: Roland
authors: R
authors: Tschismarov
authors: Yu
authors: Y
authors: Zhang
authors: Martina
authors: M
authors: Rembold
authors: Martin
authors: M
authors: Gaisberger
authors: Arnulf
authors: A
authors: Hartl
authors: Michelle M
authors: MM
authors: Epstein
authors: Patrick
authors: P
authors: Matthias
authors: Christian
authors: C
authors: Seiser
authors: Wilfried
authors: W
authors: Ellmeier
mesh_terms: D000818:Animals; D016764:Cell Polarity / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004195:Disease Models, Animal; D056284:Histone Deacetylase 1 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D007249:Inflammation / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000201:enzymology / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012130:Respiratory Hypersensitivity / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology*
chemical_list: D016207:Cytokines; C484389:Hdac1 protein, mouse; D056284:Histone Deacetylase 1