Bcl11b is essential for licensing Th2 differentiation during helminth infection and allergic asthma.

ABSTRACT: During helminth infection and allergic asthma, naive CD4⁺ T-cells differentiate into cytokine-producing Type-2 helper (Th2) cells that resolve the infection or induce asthma-associated pathology. Mechanisms regulating the Th2 differentiation in vivo remain poorly understood. Here we report that mice lacking Bcl11b in mature T-cells have a diminished capacity to mount Th2 responses during helminth infection and allergic asthma, showing reduced Th2 cytokines and Gata3, and elevated Runx3. We provide evidence that Bcl11b is required to maintain chromatin accessibility at Th2-cytokine promoters and locus-control regions, and binds the Il4 HS IV silencer, reducing its accessibility. Bcl11b also binds Gata3-intronic and downstream-noncoding sites, sustaining the Gata3 expression. In a

SUBMITTER: Lorentsen KJ 

PROVIDER: S-EPMC5920086 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature