title: The Bacterial Peptidoglycan-Sensing Molecules NOD1 and NOD2 Promote CD8+Thymocyte Selection.
abstract: Nucleotide-binding and oligomerization domain (NOD)-like receptors NOD1 and NOD2 are cytosolic innate immune receptors that recognize microbial peptidoglycans. Although studies have addressed the role of NOD proteins in innate immune responses, little attention has been given to their impact on the developing adaptive immune system. We have assessed the roles of NOD1 and NOD2 deficiency on T cell development in mice. Our results demonstrate that NOD1 and NOD2 promote the positive selection/maturation of CD8 single-positive thymocytes in a thymocyte-intrinsic manner. TCR-mediated ERK phosphorylation is significantly reduced in the absence of NOD proteins, but receptor-interacting protein 2 is not involved in CD8 single-positive thymocyte selection or ERK signaling. Commensal bacteria-free animals have thymocyte maturation defects, and exogenous NOD ligands can enhance thymocyte maturation in culture. These results raise the intriguing possibility that abnormal lymphocyte responses observed in NOD-dependent inflammatory diseases are not driven solely by microbial signals in the gut, but may also involve intrinsic lymphocyte defects resulting from impaired CD8 T cell thymic development.
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037.
authors.forename: Marianne M
authors.identifier: 0000-0003-4407-3423
authors.initials: MM
authors.lastname: Martinic
authors.affiliation: Centre for Immunology, Burnet Institute, Melbourne, Victoria 3004, Australia.|The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; and.
authors.forename: Irina
authors.initials: I
authors.lastname: Caminschi
authors.affiliation: Centre for Immunology, Burnet Institute, Melbourne, Victoria 3004, Australia.
authors.forename: Meredith
authors.initials: M
authors.lastname: O'Keeffe
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037.
authors.forename: Therese C
authors.initials: TC
authors.lastname: Thinnes
authors.forename: Raelene
authors.initials: R
authors.lastname: Grumont
authors.forename: Steve
authors.initials: S
authors.lastname: Gerondakis
authors.affiliation: Division of Nephrology, Department of Medicine, University of California San Diego, La Jolla, CA 92093.
authors.forename: Dianne B
authors.identifier: 0000-0002-4857-6039
authors.initials: DB
authors.lastname: McKay
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037.
authors.forename: David
authors.identifier: 0000-0002-4769-6311
authors.initials: D
authors.lastname: Nemazee
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037; agavin@scripps.edu.|Centre for Immunology, Burnet Institute, Melbourne, Victoria 3004, Australia.
authors.forename: Amanda L
authors.identifier: 0000-0001-9921-4225
authors.initials: AL
authors.lastname: Gavin
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D015151:Immunoblotting; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053474:Nod1 Signaling Adaptor Protein / Q000276:immunology*; D053473:Nod2 Signaling Adaptor Protein / Q000276:immunology*; D016133:Polymerase Chain Reaction; D060168:Thymocytes / Q000166:cytology* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
chemical_list: D053474:Nod1 Signaling Adaptor Protein; C507873:Nod1 protein, mouse; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse