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Critical Reviews™ in Immunology
Factor de Impacto: 1.352 Factor de Impacto de 5 años: 3.347 SJR: 1.022 SNIP: 0.55 CiteScore™: 2.19

ISSN Imprimir: 1040-8401
ISSN En Línea: 2162-6472

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Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v31.i3.40
pages 233-263

Function of Histone Deacetylase Inhibitors in Inflammation

Aleksander M. Grabiec
Division of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, Room K0-140, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
Paul P. Tak
Division of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, Room K0-140, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
Kris A. Reedquist
Division of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

SINOPSIS

Histone deacetylases (HDACs) display multi-faceted roles in coordinating the interaction of intracellular signaling pathways with chromatin remodeling and transcription factor function to finely specify gene alterations and maintenance of gene expression during cellular activation, proliferation, and differentiation. These processes, epigenetic and non-epigenetic, are critical to the development of both the adaptive and innate arms of the mammalian immune system, and the measured initiation and resolution of immune responses. Pharmacological modulators of HDAC activity have demonstrated uniformly potent anti-inflammatory effects in experimental animal models of these diseases, in relevant immune and stromal cell populations from patients, as well as initial successes in the clinic. Recent studies have identified key roles for specific HDACs in regulating immune function, as well as alterations in HDAC expression and function in a number of immune-mediated inflammatory diseases (IMIDs), which may contribute to pathology in these diseases. Here, we review recent advances in our understanding of HDAC function in the immune system, their contribution to IMIDs, and the therapeutic potential of altering HDAC activity in IMIDs.


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