Divergent roles of histone deacetylase 6 (HDAC6) and histone deacetylase 11 (HDAC11) on the transcriptional regulation of IL10 in antigen presenting cells.

Abstract:

:The anti-inflammatory cytokine IL-10 is a key modulator of immune responses. A better understanding of the regulation of this cytokine offers the possibility of tipping the balance of the immune response toward either tolerance, or enhanced immune responses. Histone deacetylases (HDACs) have been widely described as negative regulators of transcriptional regulation, and in this context, the primarily nuclear protein HDAC11 was shown to repress il-10 gene transcriptional activity in antigen-presenting cells (APCs). Here we report that another HDAC, HDAC6, primarily a cytoplasmic protein, associates with HDAC11 and modulates the expression of IL-10 as a transcriptional activator. To our knowledge, this is the first demonstration of two different HDACs being recruited to the same gene promoter to dictate divergent transcriptional responses. This dynamic interaction results in dynamic changes in the expression of IL-10 and might help to explain the intrinsic plasticity of the APC to determine T-cell activation versus T-cell tolerance.

journal_name

Mol Immunol

journal_title

Molecular immunology

authors

Cheng F,Lienlaf M,Perez-Villarroel P,Wang HW,Lee C,Woan K,Woods D,Knox T,Bergman J,Pinilla-Ibarz J,Kozikowski A,Seto E,Sotomayor EM,Villagra A

doi

10.1016/j.molimm.2014.02.019

subject

Has Abstract

pub_date

2014-07-01 00:00:00

pages

44-53

issue

1

eissn

0161-5890

issn

1872-9142

journal_volume

60

pub_type

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