Investigating the role of ERK2 in peripheral T cell function using a novel transgenic mouse model

Extracellular signal Regulated Kinase 2 (ERK2) is an important Serine-Threonine Kinase involved in the Mitogen Activated Protein Kinase (MAPK) pathway. ERK2 is indispensable for early T cell development and is also believed to play a role in T-cell specific antigen recognition, signaling, cell proliferation, differentiation, migration and survival. However, it remains unclear how ERK2 regulates peripheral T cell function. Our studies focused on the impact and mechanism of ERK2 deficiency in peripheral T cell activation/function utilizing a mouse model with a conditional ERK2 knockout identified and confirmed by expression of a Yellow Fluorescent Protein (YFP) reporter. Our gene knockout strategy relied on Cre recombinase driven by either proximal lck or inducible promoters. Using flow cytometry analysis/cell sorting and cytokine ELISPOT assay, we have found that T cell activation, survival and cytokine production were impaired in the absence of ERK2. Our results also indicate a role for ERK2 in cell survival in serum starvation and ionomycin/Ca2+ mediated apoptosis. In addition, we characterized the activation marker profile of the CD4+ T cells upon ERK2 deletion. We observed an up-regulation of CD25 and Foxp3 expression, which could suggest a role for ERK2 in affecting the stability of "nTreg" cells. The presented approach will allow us to further investigate the role of ERK2 in other peripheral T cell functions and potentially identify cellular signaling pathways that could be explored for the treatment of CD4+ T cell mediated autoimmune diseases such as multiple sclerosis (MS).