title: NOD1 cooperates with TLR2 to enhance T cell receptor-mediated activation in CD8 T cells.
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-κB, 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.
authors: Université de Lyon, Lyon, France. blandinemercier7@gmail.com
authors: Blandine C
authors: BC
authors: Mercier
authors: Erwan
authors: E
authors: Ventre
authors: Marie-Laure
authors: ML
authors: Fogeron
authors: Anne-Laure
authors: AL
authors: Debaud
authors: Martine
authors: M
authors: Tomkowiak
authors: Jacqueline
authors: J
authors: Marvel
authors: Nathalie
authors: N
authors: Bonnefoy
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008024:Ligands; D020935:MAP Kinase Signaling System; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D053474:Nod1 Signaling Adaptor Protein / Q000378:metabolism*; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2 / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D008024:Ligands; D016328:NF-kappa B; C119067:NOD1 protein, human; D053474:Nod1 Signaling Adaptor Protein; C507873:Nod1 protein, mouse; D011948:Receptors, Antigen, T-Cell; C495342:TLR2 protein, human; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; C506253:RIPK2 protein, human; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases