The role of ERK2 in dendritic cell function

Abstract

Abstract Dendritic cells (DCs) are an important link between the innate and adaptive immune systems, specifically by serving as key regulators of T cell-dependent (TD) immune responses. In DCs, several processes critical for initiating TD immune responses, such as migration, provision of costimulatory signals, and antigen uptake and presentation, utilize the mitogen-activated protein kinase (MAPK) signaling pathway. The dysregulation of these processes can result in the aberrant activation of autoreactive CD4+ T cells, resulting in autoimmune disease. Extracellular signal-regulated kinase 1 and 2 (ERK1/2) are key effectors of the MAPK pathway, and while ERK1 has been shown to be a critical regulator of DC migration and TLR-induced IL-10 secretion, the function of ERK2 remains unknown. Our lab has developed a novel mouse model in which the inducible Cre-mediated deletion of Erk2 is accompanied by the expression of an eYFP reporter protein. This provides us the unique ability to circumvent the embryonic lethality of deleting Erk2 in the germline while also allowing the detection of viable Erk2-deficient cells via flow cytometry. Preliminary data using this model has shown that Erk2Δ bone marrow-derived DCs (BMDCs), as well as Erk2Δ splenic DCs, exhibit altered expression of surface markers associated with T cell costimulation, antigen presentation, and migration compared with DCs from littermate controls. Taken together, this suggests that ERK2 plays a unique role in the regulation of several DC functions, potentially opening a new approach to treating CD4+ T cell-mediated autoimmune diseases.