nod1 cooperates with tlr2 to enhance t cell receptor-mediated activation in cd8 t cellsnod1与tlr2合作增强t细胞受体介导,cd8 t细胞的活化.pdfVIP

NOD1 Cooperates with TLR2 to Enhance T Cell Receptor- Mediated Activation in CD8 T Cells Blandine C. Mercier1,2,3*, Erwan Ventre 1,2,3., Marie-Laure Fogeron1,2,3., Anne-Laure Debaud1,2,3, Martine Tomkowiak1,2,3, Jacqueline Marvel1,2,3, Nathalie Bonnefoy1,2,3,4* ´ ´ ´ ´ 1 Universite de Lyon, Lyon, France, 2 Institut National de la Sante et de la Recherche Medicale, U851, Lyon, France, 3 Universite Lyon 1, Lyon, France, 4 Hospices Civils de Lyon, Lyon, France Abstract Pattern recognition receptors (PRR), like Toll-like receptors (TLR) and NOD-like receptors (NLR), are involved in the detection of microbial infections and tissue damage by cells of the innate immune system. Recently, we and others have demonstrated that TLR2 can additionally function as a costimulatory receptor on CD8 T cells. Here, we establish that the intracytosolic receptor NOD1 is expressed and functional in CD8 T cells. We show that C12-iEDAP, a synthetic ligand for NOD1, has a direct impact on both murine and human CD8 T cells, increasing proliferation and effector functions of cells activated via their T cell receptor (TCR). This effect is dependent on the adaptor molecule RIP2 and is associated with an increased activation of the NF-kB, JNK and p38 signaling pathways. Furthermore, we demonstrate that NOD1 stimulation can cooperate with TLR2 engagement on CD8 T cells to enhance TCR-mediated activation. Altogether our results indicate that NOD1 might function as an alternative costimulatory receptor in CD8 T cells. Our study provides new insights into the function of NLR in T cells and extends to NOD1 the recent concept that PRR stimulation can directly control T cell functions. Citation: Mercier BC, Ventre E, Fogeron M-L, Debaud A-L, Tomkowia