HnRNPL is essential for T cell function in the Periphery

Abstract

Abstract While RNA binding proteins (RBPs) have recently emerged as regulators of gene expression in immune cells, their effect on T cell fate needs further investigation. Heterogeneous Nuclear Ribonucleoprotein (hnRNPs) are RBPs that play a crucial role in many aspects of RNA biogenesis, alternative splicing, expression, and function. During T cell development hnRNPL is known to regulate the proliferation, and migration of thymic pre-T cells, as loss of hnRNPL in early T cell development results in a failure of T cells to reach the periphery. Little is known about how hnRNPL affects T cell activation, and function. Our lab has used CD4 Cre × hnRNPL Fl/Fl(KO) mice to understand the role of hnRNPL in peripheral T cells. Our initial study of the steady state profile of the KO mice shows normal migration of T cells form the thymus, but there is a reduction in peripheral T cell numbers. We also show that hnRNPL plays an important role in T cell activation and survival, since T cells lacking hnRNPL do not survive long enough to differentiate into T helper cell subsets. In vivo, using immunization studies, we show that KO CD4 T cells fail to fully differentiate into Tfh and are unable to support the formation of germinal center B cells. To ensure the effect that hnRNPL has on T cells in the periphery is not caused by the loss of hnRNPL during thymic T cell development we are using the CD4-Cre/ERT2 × hnRNPL (I-KO) to investigate how the loss of hnRNPL in peripheral T cell affects the ability of T cells to differentiate and survive post activation. Further studies will also focus on the mechanisms hnRNPL use to regulate T cells activation and survival. These studies suggest that hnRNPL plays an important role in the activation and survival of peripheral T cells. AAI Fellowship