Anti-IL2RA monoclonal antibody, clone QD72.6.4 [Biotin]

This meta-analysis studied the association between interleukin 2 receptor alpha (IL2RA) gene polymorphisms rs2104286 and rs12722489 and susceptibility to multiple sclerosis (MS). Case control genetic association studies published before January 2011 were retrieved from the PubMed and EMBASE databases and the Cochrane Library. Eight studies comprising 13 569 patients and 23 435 controls met the selection criteria for meta-analysis of the IL2RA rs2104286 polymorphism. Using a fixed-effects model, the T allele and the TT and TT + TC genotypes of the IL2RA rs2104286 polymorphism were found to be associated with MS. Five studies comprising 5643 patients and 6415 controls met the selection criteria for meta-analysis of the IL2RA rs12722489 polymorphism. Using a fixed-effects model, the C allele and the CC genotype of the IL2RA rs12722489 polymorphism were found to be associated with MS but the CC + CT genotype was not. It was concluded that both of the IL2RA gene polymorphisms, rs2104286 and rs12722489, were associated with increased susceptibility to MS.

Cytokines critically control immune responses, but how regulatory programs are altered to allow T cells to differentially respond to distinct cytokine stimuli remains poorly understood. Here, we have globally analyzed enhancer elements bound by IL-2-activated STAT5 and IL-21-activated STAT3 in T cells and identified Il2ra as the top-ranked gene regulated by an IL-2-activated STAT5-bound superenhancer and one of the top genes regulated by STAT3-bound superenhancers. Moreover, we found that STAT5 binding was rapidly superenriched at genes highly induced by IL-2 and that IL-2-activated STAT5 binding induces new and augmented chromatin interactions within superenhancer-containing genes. Based on chromatin interaction analysis by paired-end tag (ChIA-PET) sequencing data, we used CRISPR-Cas9 gene editing to target three of the STAT5 binding sites within the Il2ra superenhancer in mice. Each mutation decreased STAT5 binding and altered IL-2-induced Il2ra gene expression, revealing that individual elements within the superenhancer were not functionally redundant and that all were required for normal gene expression. Thus, we demonstrate cooperative utilization of superenhancer elements to optimize gene expression and show that STAT5 mediates IL-2-induced chromatin looping at superenhancers to preferentially regulate highly inducible genes, thereby providing new insights into the mechanisms underlying cytokine-dependent superenhancer function.