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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\u2013free 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.<\/jats:p>","DOI":"10.4049\/jimmunol.1601462","type":"journal-article","created":{"date-parts":[[2017,2,16]],"date-time":"2017-02-16T01:40:26Z","timestamp":1487209226000},"page":"2649-2660","source":"Crossref","is-referenced-by-count":32,"title":["The Bacterial Peptidoglycan-Sensing Molecules NOD1 and NOD2 Promote CD8+ Thymocyte Selection"],"prefix":"10.1093","volume":"198","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4407-3423","authenticated-orcid":false,"given":"Marianne M","family":"Martinic","sequence":"first","affiliation":[{"name":"Department of Immunology and Microbial Science, The Scripps Research Institute , La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Caminschi","sequence":"additional","affiliation":[{"name":"Centre for Immunology, Burnet Institute , Melbourne, Victoria 3004,","place":["Australia"]},{"name":"The Walter and Eliza Hall Institute of Medical Research , Parkville, Victoria 3052,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meredith","family":"O\u2019Keeffe","sequence":"additional","affiliation":[{"name":"Centre for Immunology, Burnet Institute , Melbourne, Victoria 3004,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Therese C","family":"Thinnes","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbial Science, The Scripps Research Institute , La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raelene","family":"Grumont","sequence":"additional","affiliation":[{"name":"Centre for Immunology, Burnet Institute , Melbourne, Victoria 3004,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Gerondakis","sequence":"additional","affiliation":[{"name":"Centre for Immunology, Burnet Institute , Melbourne, Victoria 3004,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4857-6039","authenticated-orcid":false,"given":"Dianne B","family":"McKay","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, University of California San Diego , La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4769-6311","authenticated-orcid":false,"given":"David","family":"Nemazee","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbial Science, The Scripps Research Institute , La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9921-4225","authenticated-orcid":false,"given":"Amanda L","family":"Gavin","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbial Science, The Scripps Research Institute , La Jolla, CA 92037"},{"name":"Centre for Immunology, Burnet Institute , Melbourne, Victoria 3004,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,4,1]]},"reference":[{"key":"2025030615080112200_r1","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1038\/ni945","article-title":"An essential role for NOD1 in host recognition of bacterial peptidoglycan containing diaminopimelic acid","volume":"4","author":"Chamaillard","year":"2003","journal-title":"Nat. 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