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: Reinhard Grausenburger, Ivan Bilic, Nicole Boucheron, Gordin Zupkovitz, Lamia El-Housseiny, Roland Tschismarov, Yu Zhang, Martina Rembold, Martin Gaisberger, Arnulf Hartl, Michelle M Epstein, Patrick Matthias, Christian Seiser, Wilfried Ellmeier
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 185 Issue 6 Pg. 3489-97 (Sep 15 2010) ISSN: 1550-6606 [Electronic] United States
• PMID: 20702731 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Hdac1 protein, mouse
• Histone Deacetylase 1

Topics

• Animals
• Cell Polarity (genetics, immunology)
• Cells, Cultured
• Cytokines (biosynthesis)
• Disease Models, Animal
• Histone Deacetylase 1 (deficiency, genetics, physiology)
• Inflammation (enzymology, genetics, immunology)
• Lung (enzymology, immunology, pathology)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Respiratory Hypersensitivity (enzymology, immunology, pathology)
• Th1 Cells (enzymology, immunology, pathology)
• Th2 Cells (enzymology, immunology, pathology)
• Up-Regulation (genetics, immunology)