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Divergent roles of histone deacetylase 6 (HDAC6) and histone deacetylase 11
(HDAC11) on the transcriptional regulation of IL10 in antigen presenting cells
#MMPMID24747960
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
Mol Immunol
2014[Jul]; 60
(1
): 44-53
PMID24747960
show ga
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.
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