{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T03:57:33Z","timestamp":1770091053411,"version":"3.49.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2003,6,1]],"date-time":"2003-06-01T00:00:00Z","timestamp":1054425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>IL-10-deficient mice exhibit spontaneous enterocolitis and other symptoms akin to Crohn\u2019s disease, indicating that IL-10 might regulate normal physiology in the gut. However, clinical trials with IL-10 in Crohn\u2019s disease were disappointing, although some patients showed healing of intestinal mucosa. This study searched for genetic polymorphisms within the IL-10 pathway. We decided to screen for mutations of the IL-10R1 cDNA in healthy volunteers and Crohn\u2019s disease patients and identified two novel variants: a serine 138-to-glycine (S138G) and a glycine 330-to-arginine (G330R) substitution. The allelic frequency in a European cohort was relatively high (16% for the S138G and 33% for the G330R), and S138G was in strong linkage disequilibrium with G330R. A similar allele frequency was found in a group of Crohn\u2019s patients. In IL-10R1 G330R-expressing monocytes, the inhibitory effect of IL-10 on TNF-\u03b1 production was diminished, indicating that this variant may be a loss-of-function allele. No such difference was observed between haplotypes 4 (G330R only) and 7 (S138G and G330R). In addition, these IL-10R1 variants had no influence on the IL-10R1 expression density. Structural analysis of the S138G variant revealed that the substitution of S138G may interfere with binding of IL-10 to IL-10R1.<\/jats:p>","DOI":"10.4049\/jimmunol.170.11.5578","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T20:09:10Z","timestamp":1398024550000},"page":"5578-5582","source":"Crossref","is-referenced-by-count":52,"title":["Novel Variants of the IL-10 Receptor 1 Affect Inhibition of Monocyte TNF-\u03b1 Production"],"prefix":"10.1093","volume":"170","author":[{"given":"Christoph","family":"Gasche","sequence":"first","affiliation":[{"name":"Department of Medicine 4, Division of Gastroenterology and Hepatology, University of Vienna , Vienna ,","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Grundtner","sequence":"additional","affiliation":[{"name":"Department of Medicine 4, Division of Gastroenterology and Hepatology, University of Vienna , Vienna ,","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petra","family":"Zwirn","sequence":"additional","affiliation":[{"name":"Department of Medicine 4, Division of Gastroenterology and Hepatology, University of Vienna , Vienna ,","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Walter","family":"Reinisch","sequence":"additional","affiliation":[{"name":"Department of Medicine 4, Division of Gastroenterology and Hepatology, University of Vienna , Vienna ,","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah H","family":"Shaw","sequence":"additional","affiliation":[{"name":"DNA Sciences, Inc. , Fremont, CA 94555"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Zdanov","sequence":"additional","affiliation":[{"name":"Macromolecular Crystallography Laboratory, National Cancer Institute , Frederick, MD 21702"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Usha","family":"Sarma","sequence":"additional","affiliation":[{"name":"Imperial College School of Medicine, Kennedy Institute of Rheumatology , London ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lynn M","family":"Williams","sequence":"additional","affiliation":[{"name":"Imperial College School of Medicine, Kennedy Institute of Rheumatology , London ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian M","family":"Foxwell","sequence":"additional","affiliation":[{"name":"Imperial College School of Medicine, Kennedy Institute of Rheumatology , London ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfred","family":"Gangl","sequence":"additional","affiliation":[{"name":"Department of Medicine 4, Division of Gastroenterology and Hepatology, University of Vienna , Vienna ,","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2003,6,1]]},"reference":[{"key":"2026020210132837100_R1","first-page":"683","volume-title":"Annu. Rev. Immunol.","year":"2001"},{"key":"2026020210132837100_R2","first-page":"263","volume-title":"Cell","year":"1993"},{"key":"2026020210132837100_R3","first-page":"389","volume-title":"J. Leukocyte Biol.","year":"1997"},{"key":"2026020210132837100_R4","first-page":"121","volume-title":"Am. J. Pathol.","year":"1998"},{"key":"2026020210132837100_R5","first-page":"3815","volume-title":"J. Immunol.","year":"1991"},{"key":"2026020210132837100_R6","first-page":"1209","volume-title":"J. Exp. Med.","year":"1991"},{"key":"2026020210132837100_R7","first-page":"573","volume-title":"Gastroenterology","year":"1998"},{"key":"2026020210132837100_R8","first-page":"21053","volume-title":"J. Biol. Chem.","year":"1993"},{"key":"2026020210132837100_R9","first-page":"11267","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1993"},{"key":"2026020210132837100_R10","first-page":"1821","volume-title":"J. Immunol.","year":"1994"},{"key":"2026020210132837100_R11","first-page":"571","volume-title":"J. Exp. Med.","year":"1998"},{"key":"2026020210132837100_R12","first-page":"5894","volume-title":"EMBO J.","year":"1997"},{"key":"2026020210132837100_R13","first-page":"1079","volume-title":"J. Immunol.","year":"1995"},{"key":"2026020210132837100_R14","first-page":"1349","volume-title":"Science","year":"1995"},{"key":"2026020210132837100_R15","first-page":"1630","volume-title":"Science","year":"1997"},{"key":"2026020210132837100_R16","first-page":"563","volume-title":"J. Interferon Cytokine Res.","year":"1999"},{"key":"2026020210132837100_R17","first-page":"16513","volume-title":"J. Biol. Chem.","year":"1999"},{"key":"2026020210132837100_R18","first-page":"39","volume-title":"Immunity","year":"1999"},{"key":"2026020210132837100_R19","first-page":"362","volume-title":"J. Clin. Immunol.","year":"2000"},{"key":"2026020210132837100_R20","first-page":"383","volume-title":"Gastroenterology","year":"1997"},{"key":"2026020210132837100_R21","first-page":"1473","volume-title":"Gastroenterology","year":"2000"},{"key":"2026020210132837100_R22","first-page":"1461","volume-title":"Gastroenterology","year":"2000"},{"key":"2026020210132837100_R23","first-page":"28","volume-title":"Clin. Exp. Immunol.","year":"1998"},{"key":"2026020210132837100_R24","first-page":"386","volume-title":"Tissue Antigens","year":"1999"},{"key":"2026020210132837100_R25","first-page":"3578","volume-title":"Electrophoresis","year":"2000"},{"key":"2026020210132837100_R26","first-page":"439","volume-title":"Immunogenetics","year":"1997"},{"key":"2026020210132837100_R27","first-page":"1955","volume-title":"Protein Sci.","year":"1996"},{"key":"2026020210132837100_R28","first-page":"35","volume-title":"Immunity","year":"2001"},{"key":"2026020210132837100_R29","first-page":"110","volume-title":"Acta Crystallogr. A","year":"1991"},{"key":"2026020210132837100_R30","first-page":"958","volume-title":"J. Appl. Crystallogr.","year":"1991"},{"key":"2026020210132837100_R31","first-page":"188","volume-title":"Handbook of Human Genetic Linkage"},{"key":"2026020210132837100_R32","first-page":"49","volume-title":"Genetics","year":"1964"},{"key":"2026020210132837100_R33","first-page":"1142","volume-title":"Rheumatology (Oxford)","year":"1999"},{"key":"2026020210132837100_R34","first-page":"5043","volume-title":"Mol. Cell. Biol.","year":"1995"},{"key":"2026020210132837100_R35","first-page":"8","volume-title":"Inflamm. Bowel Dis.","year":"2000"},{"key":"2026020210132837100_R36","first-page":"845","volume-title":"Am. J. Hum. Genet.","year":"2002"},{"key":"2026020210132837100_R37","first-page":"A-300","volume-title":"Gastroenterology","year":"2002"},{"key":"2026020210132837100_R38","first-page":"1006","volume-title":"EMBO J.","year":"1998"},{"key":"2026020210132837100_R39","first-page":"4837","volume-title":"J. Immunol.","year":"2002"},{"key":"2026020210132837100_R40","first-page":"240","volume-title":"Nat. Med.","year":"2002"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/170\/11\/5578\/62569441\/5578.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/170\/11\/5578\/62569441\/5578.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T15:17:30Z","timestamp":1770045450000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/170\/11\/5578\/8028681"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,6,1]]},"references-count":40,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2003,6,1]]},"published-print":{"date-parts":[[2003,6,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.170.11.5578","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2003,6]]},"published":{"date-parts":[[2003,6,1]]}}}