Mapping Bcl11b binding in human regulatory T cells

T regulatory (Treg) cells have been studied in depth since their discovery for their potential use in therapies of autoimmune diseases. Treg cells have a suppression program that includes surface molecules CD25 (IL2R), cytotoxic T-lymphocyte associated protein 4 (CTLA4), and glucocorticoid-induced TNFR family (GITR) to limit aberrant and excessive inflammatory immune responses. We have shown that Bcl11b can bind to the CNS2 region in Foxp3 as well as the gene loci of those essential surface molecules for Treg suppression. Furthermore, we have identified a subset of Foxp3-independent genes in Treg cells directly regulated by Bcl11b binding. Bcl11b also directly represses expression of innate molecules such as transcription factors PU.1 and ID2 in Treg cells. Finally, we have also shown that removal of Bcl11b accelerates apoptosis in Treg cells as cleaved caspase 3 levels were significantly elevated in Bcl11b KO Treg cells when compared with WT Treg cells. Examination of Bcl11b binding in regulatory T cells from human peripheral blood

调节性T细胞（T regulatory cells，简称Treg细胞）自被发现以来，因其在自身免疫性疾病治疗中的应用潜力而受到深入研究。Treg细胞拥有一套抑制程序，该程序包含表面分子CD25（IL2Rα）、细胞毒性T淋巴细胞相关蛋白4（CTLA4）以及糖皮质激素诱导的肿瘤坏死因子受体家族（GITR），用以限制异常且过度的炎症性免疫应答。我们的研究证实，Bcl11b可结合Foxp3基因的CNS2区域，以及Treg细胞发挥抑制功能所需的上述关键表面分子的基因座。此外，我们还在Treg细胞中鉴定出一组受Bcl11b结合直接调控的Foxp3非依赖性基因。Bcl11b还可直接抑制Treg细胞中PU.1、ID2等转录因子这类先天分子的表达。最后，我们还证实，敲除Bcl11b可加速Treg细胞的凋亡：与野生型（WT）Treg细胞相比，Bcl11b敲除（KO）Treg细胞中的剪切型半胱天冬酶3（cleaved caspase 3）水平显著升高。本研究还对人外周血来源的调节性T细胞中的Bcl11b结合情况进行了检测。