Ascl2 for T_FH cells

The development of follicular helper T cells (T_FH cells) is initiated when T cells migrate into the B cell follicle as they upregulate expression of the chemokine receptor CXCR5. In Nature, Dong and colleagues show that the helix-loop-helix factor Ascl2 initiates T_FH cell development. Ascl2 expression in T_FH cells is dependent on Wnt agonists but is independent of transcription factors known to regulate T_FH cell development, such as Bcl-6, Batf and STAT5. Ascl2 induces Cxcr5 expression by directly binding to E-boxes in the Cxcr5 promoter and represses genes related to the T_H1, T_H2 and T_H17 subsets of helper T cells through a transcriptional profile distinct from that of Maf, Batf and IRF4, which are required for T_FH differentiation. Acute deletion of Ascl2 in vivo leads to total impairment of T_FH cell development and germinal center response in mice. In addition, the E-protein inhibitor Id3 inhibits Ascl2 function and the generation of T_FH cells, which suggests that E-box proteins control T_FH differentiation.

Nature (19 January 2014) doi:10.1038/nature12910