The poly(C)-binding protein Pcbp2 is essential for CD4 + T cell activation and proliferation.

The RNA-binding protein Pcbp2 is widely expressed in the innate and adaptive immune systems and is essential for mouse development. To determine whether Pcbp2 is required for CD4 T cell development and function, we derived mice with conditional Pcbp2 deletion in CD4 T cells and assessed their overall phenotype and proliferative responses to activating stimuli. We found that Pcbp2 is essential for T conventional cell (Tconv) proliferation, working through regulation of co-stimulatory signaling. Pcbp2 deficiency in the CD4 lineage did not impact Treg abundance or function . In addition, our data demonstrate a clear association between Pcbp2 control of Runx1 exon 6 splicing in CD4 T cells and a specific role for Pcbp2 in the maintenance of peripheral CD4 lymphocyte population size. Last, we show that Pcbp2 function is required for optimal Tconv cell activation in a T cell adoptive transfer colitis model system.