MEK Kinase 1 signaling regulates Natural Killer T cells (50.38)

Abstract

Abstract MEK Kinase 1 (MEKK1) is of critical importance in controlling the thymus-dependent immune response by regulating Mitogen-Activated Protein Kinase (MAPK) activation from many receptors. Natural Killer T (NKT) cells are a distinct subset of lymphocytes that are characterized by the cell surface expression of a single invariant T-cell receptor (TCR) and Natural Killer (NK) cell markers. The activation of NKT cells is initiated by the engagement of the NKT receptor with glycolipid antigens presented by the molecule CD1d. Careful examination of Mekk1 kinase-deficient mice (Mekk1ΔKD) reveals multiple defects in NKT cells. Mekk1ΔKD NKT cells have deficient: MAPK signal transduction, proliferative expansion, apoptosis, and aberrant cytokine production. Mekk1ΔKD mice display elevated liver damage in a ConA-induced acute hepatitis liver injury model. My results demonstrate for the first time that MEKK1 is a critical MAPK Kinase kinase (MAP3K) signalling component for the regulation of NKT cells.