Nave CD4+ T-helper cells differentiate into Th2 effector cells during asthma and helminth (worm) infection. Here, we report that mice lacking the transcription factor Bcl11b in mature CD4+ T-cells are incapable of mounting an effective Th2 response in asthma and worm infection, with a major reduction of Th2 cytokine secretion and GATA3 expression. We found that Bcl11b exerts its role in Th2 differentiation through several avenues: (1) association with intronic regions at the Gata3 locus, sustaining GATA3 expression; (2) binding to and restricting chromatin accessibility at the Il4 silencer, located at hypersensitivity site (HS) IV; and (3) restricting Runx3 expression by association with a regulatory region 5 of Runx3. Thus, in the absence of Bcl11b, the reduction in GATA3 levels combined with increased Runx3 levels and activity at Il4 HS IV silencer and consequently diminished IL-4 expression. This results in reduced chromatin opening at the Th2 locus control region (LCR), Il13 and Il5 promoters, subsequently preventing expression of Th2 cytokine genes and Th2 differentiation. Our results establish a novel role for Bcl11b in the regulatory loop critical for licensing the Th2 program in vivo. SOURCE: Kyle,James,Lorentsen (kyle.lorentsen@medicine.ufl.edu) - Avram University of Florida

Pluto Bioinformatics

GSE99598: Transcriptome analysis of Bcl11b-deficient CD4+ T-cells during Th2 immune response