Analysis of Map3k-dependent molecular mechanisms regulating signaling in iNKT and B cells

Abstract: Abstract Our immune system consists of two types of lymphocytes; B lymphocytes which produce antibodies in response to an antigen, and T lymphocytes which differentiate into particular effector T lymphocytes such as a cytotoxic, helper or regulatory T cell in response to an antigen. Type 1 invariant natural killer T cells (iNKT cells) are a unique population of T cells whose phenotypical, developmental and functional characteristics differ from conventional T cells (Novak and Lehuen, 2011). Mitogen-Activated Protein Kinase (MAPK) signaling is critical for T lymphocyte development and effector responses. We define the roles of Map3k1 and Map3k7 genes in Natural Killer T (NKT) cells. We identify an elevated expression of the cell cycle inhibitor Cdkn1b during the Map3k1ΔKD iNKT cell clonal burst. We find aberrant Interleukin (IL) -17 production by Map3k1ΔKD iNKT cells and altered expression of Rorc, Mmp9 and Il17rb in Map3k1ΔKD iNKT cells. The liver damage seen in Map3k1ΔKD mice could be the cause of upregulation of Il-17 and IL-1β cytokines, and IL-1β related genes (Il1r2 and Il1f9). Additionally we find that Map3k1+/ΔKD mice injected with keyhole limpet hemocyanin (KLH) display a larger population of germinal center B cells compared to Map3k1ΔKD mice suggesting an importance of Map3k1 in germinal center formation.