Abstract
Interleukin 5 (IL-5) plays a unique role in allergic inflammatory responses, and the understanding of molecular mechanisms underlying the generation of IL-5-producing cells is crucial for the regulation of allergic disorders. Differentiation of naive CD4 T cells into type-2 helper (Th2) cells is accompanied by chromatin remodeling including hyperacetylation of histones H3 and H4 in the nucleosomes associated with the IL-4, IL-13, and IL-5 genes. Histone hyperacetylation of the IL-5 gene displayed a delayed kinetics compared with that of the IL-4 and IL-13 genes, suggesting a distinct remodeling mechanism for the IL-5-gene locus. Here we studied the role of CD28 costimulation in the generation of IL-5-producing cells and the histone hyperacetylation of the IL-5 gene locus. CD28-costimulation selectively enhanced histone hyperacetylation of the IL-5 gene locus that appeared to be mediated through NF-kappaB activation and subsequent up-regulation of GATA3. The CD28 costimulation-sensitive histone hyperacetylation spanned almost the entire intergenic region between the IL-5 and RAD50 accompanied with intergenic transcript. Thus, this is the first demonstration that CD28 costimulation controls a chromatin-remodeling process during Th2 cell differentiation.
Highlights
CD28 costimulation enhances Th2 responses significantly [16, 17]
In this report we demonstrated that CD28 costimulation controls Th2-specific histone hyperacetylation of the Interleukin 5 (IL-5) gene locus
CD28-mediated activation of NF-B and the resulting enhancement of GATA3 induction appeared to be a mechanism by which histone hyperacetylation of the IL-5 gene locus was efficiently induced
Summary
CD28 costimulation enhances Th2 responses significantly [16, 17]. Upon anti-CD28 mAb stimulation, phosphatidylinosiUpon antigen recognition by T cell receptor (TCR), naive tol 3-kinase is recruited to CD28 and activated, and sub-. We reported that demethylation of this region is regulated by polycomb group genes [32] that are known to cells; IFN, interferon; STAT, signal transducers and activators of transcription; IL, interleukin; mAb, monoclonal antibody; ELISA, enzymelinked immunosorbent assay; CNS1, conserved noncoding sequence 1; EGFP, enhanced GFP; RT, reverse transcription; IRES, internal ribo-. This paper is available on line at http://www.jbc.org
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