{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:55:22Z","timestamp":1791352522804,"version":"4.3.1"},"reference-count":36,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5710","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2005,2,4]]},"abstract":"<jats:p>The gene encoding the Nod2 protein is frequently mutated in Crohn's disease (CD) patients, although the physiological function of Nod2 in the intestine remains elusive. Here we show that protective immunity mediated by Nod2 recognition of bacterial muramyl dipeptide is abolished in Nod2-deficient mice. These animals are susceptible to bacterial infection via the oral route but not through intravenous or peritoneal delivery. Nod2 is required for the expression of a subgroup of intestinal anti-microbial peptides, known as cryptdins. The Nod2 protein is thus a critical regulator of bacterial immunity within the intestine, providing a possible mechanism for Nod2 mutations in CD.<\/jats:p>","DOI":"10.1126\/science.1104911","type":"journal-article","created":{"date-parts":[[2005,2,3]],"date-time":"2005-02-03T17:43:14Z","timestamp":1107452594000},"page":"731-734","source":"Crossref","is-referenced-by-count":1525,"title":["Nod2-Dependent Regulation of Innate and Adaptive Immunity in the Intestinal Tract"],"prefix":"10.1126","volume":"307","author":[{"given":"Koichi S.","family":"Kobayashi","sequence":"first","affiliation":[{"name":"Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA."},{"name":"The Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA."},{"name":"Department of Pathology, The University of Michigan Medical School, Ann Arbor, MI 48109, USA."},{"name":"Comprehensive Cancer Center, The University of Michigan Medical School, Ann Arbor, MI 48109, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Chamaillard","sequence":"additional","affiliation":[{"name":"Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA."},{"name":"The Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA."},{"name":"Department of Pathology, The University of Michigan Medical School, Ann Arbor, MI 48109, USA."},{"name":"Comprehensive Cancer Center, The University of Michigan Medical School, Ann Arbor, MI 48109, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasunori","family":"Ogura","sequence":"additional","affiliation":[{"name":"Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA."},{"name":"The Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA."},{"name":"Department of Pathology, The University of Michigan Medical School, Ann Arbor, MI 48109, USA."},{"name":"Comprehensive Cancer Center, The University of Michigan Medical School, Ann Arbor, MI 48109, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Octavian","family":"Henegariu","sequence":"additional","affiliation":[{"name":"Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA."},{"name":"The Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA."},{"name":"Department of Pathology, The University of Michigan Medical School, Ann Arbor, MI 48109, USA."},{"name":"Comprehensive Cancer Center, The University of Michigan Medical School, Ann Arbor, MI 48109, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naohiro","family":"Inohara","sequence":"additional","affiliation":[{"name":"Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA."},{"name":"The Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA."},{"name":"Department of Pathology, The University of Michigan Medical School, Ann Arbor, MI 48109, USA."},{"name":"Comprehensive Cancer Center, The University of Michigan Medical School, Ann Arbor, MI 48109, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Nun\u0303ez","sequence":"additional","affiliation":[{"name":"Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA."},{"name":"The Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA."},{"name":"Department of Pathology, The University of Michigan Medical School, Ann Arbor, MI 48109, USA."},{"name":"Comprehensive Cancer Center, The University of Michigan Medical School, Ann Arbor, MI 48109, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Flavell","sequence":"additional","affiliation":[{"name":"Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA."},{"name":"The Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA."},{"name":"Department of Pathology, The University of Michigan Medical School, Ann Arbor, MI 48109, USA."},{"name":"Comprehensive Cancer Center, The University of Michigan Medical School, Ann Arbor, MI 48109, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/35079114"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/35079107"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C200673200"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C200651200"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh182"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)05063-7"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M008072200"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5396.2085"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.189.4.615"},{"key":"e_1_3_2_11_2","doi-asserted-by":"crossref","first-page":"3749","DOI":"10.4049\/jimmunol.162.7.3749","volume":"162","year":"1999","unstructured":"K. Hoshino et al., J. Immunol.162, 3749 (1999).","journal-title":"J. Immunol."},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5428.736"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/35099560"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M206473200"},{"key":"e_1_3_2_15_2","first-page":"337","volume":"8","year":"2002","unstructured":"H. Takada, S. Yokoyama, S. Yang, J. Endotoxin Res.8, 337 (2002).","journal-title":"J. Endotoxin Res."},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1092"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni712"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni758"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/77783"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(03)00661-9"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.52.11.1591"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.60.9.3556-3565.1992"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)17058-X"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)17071-2"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.62.11.5040-5047.1994"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.12.6643-6651.1999"},{"key":"e_1_3_2_27_2","first-page":"G68","volume":"271","year":"1996","unstructured":"D. Darmoul, A. J. Ouellette, Am. J. Physiol.271, G68 (1996).","journal-title":"Am. J. Physiol."},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/12.5.691"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4906(02)02246-9"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5437.113"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.32413"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.32415"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1086\/339432"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)08590-2"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2004-813072"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2003.032805"},{"key":"e_1_3_2_37_2","unstructured":"The authors thank C. L. Stewart for providing reagents; L. Evangelisti M. Chen and A. Ferrandino for technical assistance; and F. Manzo for manuscript preparation. Supported by grants from NIH (K.S.K. N.I. G.N. and R.A.F.) the Crohn's and Colitis Foundation of America (K.S.K. M.C. Y.O. and R.A.F.) the Ellison Foundation (R.A.F.) and the Eli and Edythe L. Broad Foundation (K.S.K. and G.N.). R.A.F. is an investigator of the Howard Hughes Medical Institute."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1104911","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T21:02:04Z","timestamp":1704834124000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1104911"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,2,4]]},"references-count":36,"journal-issue":{"issue":"5710","published-print":{"date-parts":[[2005,2,4]]}},"alternative-id":["10.1126\/science.1104911"],"URL":"https:\/\/doi.org\/10.1126\/science.1104911","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1023817.284815","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1023817.297898","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1023817.282697","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1023817.282699","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1023817.282703","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1023817.285804","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1023817.290713","asserted-by":"object"}]},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,2,4]]}}}