The role of ERK2 in bone marrow-derived dendritic cells development and function

Abstract

Abstract Dendritic cells (DCs) regulate antigen-specific T cell responses by providing stimulatory or inhibitory signals through surface receptors and cytokines, the expression of which relies on the mitogen-activated protein kinase (MAPK) signaling pathway. In lymphocytes, the MAPK pathway is involved in differentiation, proliferation, and survival, using extracellular signal regulated kinases 1 and 2 (ERK1/2) as primary effector molecules. Importantly, ERK1 and ERK2 are not functionally redundant, despite 85% sequence homology. The role of ERK1 in DCs has been explored, however that of ERK2 remains unknown due to the lack of Erk2 Δ transgenic models. Our lab has developed a novel mouse model in which Cre-mediated deletion of Erk2 is accompanied by the expression of an eYFP reporter gene, allowing us to identify and isolate viable Erk2 Δ cells using flow cytometry. Preliminary data has shown that DCs cultured from bone marrow progenitor cells (BMDCs) exhibit altered expression of several surface receptors associated with both antigen presentation and T cell stimulation when compared to wild type BMDCs. We therefore hypothesize that ERK2 deficiency will significantly affect the ability of DCs to prime naïve T cells. We are currently investigating the functional competency of these BMDCs regarding migration, cytokine secretion, and antigen presentation. Our results will help to elucidate the role ERK2 plays in regulating DC function, potentially offering a new approach to treating T cell-driven diseases.