The role of the ERK MAP kinase pathway in CD4 T cell proliferation and differentiation

Abstract

The ERK (Extracellular signal‐regulated protein kinase) signaling pathway is thought to be critical for T cell survival, death, proliferation and differentiation. We used germline ERK1 knockout mice and tamoxifen‐regulated conditional ERK2 knockout mice to identify the role of these two major ERK isoforms within mature CD4 T cells. Our in vitro studies revealed that ERK1 was dispensable for most aspects of CD4 T cell activation, while ERK2 performed several non‐redundant functions. We observed that ERK2 supported early CD4 T cell proliferation, as well as the differentiation of Th1, but not Th2 or Th17 cells. In addition, virus‐specific Th1 responses in the absence of ERK2 were greatly impaired, demonstrating that ERK2 also plays an important role in CD4 T cell proliferation and differentiation in vivo.