{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T00:02:38Z","timestamp":1793059358314,"version":"4.5.0"},"reference-count":36,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,4,8]],"date-time":"2013-04-08T00:00:00Z","timestamp":1365379200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2013,5]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    Bile acids (\n                    <jats:styled-content style=\"fixed-case\">BA<\/jats:styled-content>\n                    s) play important roles not only in lipid metabolism, but also in signal transduction.\n                    <jats:styled-content style=\"fixed-case\">TGR<\/jats:styled-content>\n                    5, a transmembrane receptor of\n                    <jats:styled-content style=\"fixed-case\">BA<\/jats:styled-content>\n                    s, is an immunomodulative factor, but its detailed mechanism remains unclear. Here, we aimed to delineate how\n                    <jats:styled-content style=\"fixed-case\">BA<\/jats:styled-content>\n                    s operate in immunological responses via the\n                    <jats:styled-content style=\"fixed-case\">TGR<\/jats:styled-content>\n                    5 pathway in human mononuclear cell lineages. We examined\n                    <jats:styled-content style=\"fixed-case\">TGR<\/jats:styled-content>\n                    5 expression in human peripheral blood monocytes, several types of\n                    <jats:italic>in vitro<\/jats:italic>\n                    differentiated macrophages (M\u03d5s) and dendritic cells. M\u03d5s differentiated with macrophage colony\u2010stimulating factor and interferon\u2010\u03b3 (M\u03b3\u2010M\u03d5s), which are similar to the human intestinal lamina propria\n                    <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>\n                    14\n                    <jats:sup>+<\/jats:sup>\n                    M\u03d5s that contribute to Crohn's disease (\n                    <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>\n                    ) pathogenesis by production of pro\u2010inflammatory cytokines, highly expressed\n                    <jats:styled-content style=\"fixed-case\">TGR<\/jats:styled-content>\n                    5 compared with any other type of differentiated M\u03d5 and dendritic cells. We also showed that a\n                    <jats:styled-content style=\"fixed-case\">TGR<\/jats:styled-content>\n                    5 agonist and two types of\n                    <jats:styled-content style=\"fixed-case\">BA<\/jats:styled-content>\n                    s, deoxycholic acid and lithocholic acid, could inhibit tumour necrosis factor\u2010\u03b1 production in M\u03b3\u2010M\u03d5s stimulated by commensal bacterial antigen or lipopolysaccharide. This inhibitory effect was mediated by the\n                    <jats:styled-content style=\"fixed-case\">TGR<\/jats:styled-content>\n                    5\u2013\n                    <jats:styled-content style=\"fixed-case\">cAMP<\/jats:styled-content>\n                    pathway to induce phosphorylation of c\u2010\n                    <jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>\n                    os that regulated nuclear factor\u2010\u03ba\n                    <jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>\n                    p65 activation. Next, we analysed\n                    <jats:styled-content style=\"fixed-case\">TGR<\/jats:styled-content>\n                    5 levels in lamina propria mononuclear cells (\n                    <jats:styled-content style=\"fixed-case\">LPMC<\/jats:styled-content>\n                    s) obtained from the intestinal mucosa of patients with\n                    <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>\n                    . Compared with non\u2010inflammatory bowel disease, inflamed\n                    <jats:styled-content style=\"fixed-case\">CD LPMC<\/jats:styled-content>\n                    s contained more\n                    <jats:styled-content style=\"fixed-case\">TGR<\/jats:styled-content>\n                    5 transcripts. Among\n                    <jats:styled-content style=\"fixed-case\">LPMC<\/jats:styled-content>\n                    s, isolated\n                    <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>\n                    14\n                    <jats:sup>+<\/jats:sup>\n                    intestinal M\u03d5s from patients with\n                    <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>\n                    expressed\n                    <jats:styled-content style=\"fixed-case\">TGR<\/jats:styled-content>\n                    5. In isolated intestinal\n                    <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>\n                    14\n                    <jats:sup>+<\/jats:sup>\n                    M\u03d5s, a\n                    <jats:styled-content style=\"fixed-case\">TGR<\/jats:styled-content>\n                    5 agonist could inhibit tumour necrosis factor\u2010\u03b1 production. These results indicate that\n                    <jats:styled-content style=\"fixed-case\">TGR<\/jats:styled-content>\n                    5 signalling may have the potential to modulate immune responses in inflammatory bowel disease.\n                  <\/jats:p>","DOI":"10.1111\/imm.12045","type":"journal-article","created":{"date-parts":[[2013,4,8]],"date-time":"2013-04-08T22:32:44Z","timestamp":1365460364000},"page":"19-29","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":228,"title":["<scp>TGR<\/scp>\n                    5 signalling inhibits the production of pro\u2010inflammatory cytokines by\n                    <i>in vitro<\/i>\n                    differentiated inflammatory and intestinal macrophages in Crohn's disease"],"prefix":"10.1111","volume":"139","author":[{"given":"Kazuaki","family":"Yoneno","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology Department of Internal Medicine School of Medicine Keio University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadakazu","family":"Hisamatsu","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Department of Internal Medicine School of Medicine Keio University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuyoshi","family":"Shimamura","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Department of Internal Medicine School of Medicine Keio University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhiko","family":"Kamada","sequence":"additional","affiliation":[{"name":"Department of Pathology and Comprehensive Cancer Center The University of Michigan Medical School Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riko","family":"Ichikawa","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Department of Internal Medicine School of Medicine Keio University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina T.","family":"Kitazume","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Department of Internal Medicine School of Medicine Keio University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maiko","family":"Mori","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Department of Internal Medicine School of Medicine Keio University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michihide","family":"Uo","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Department of Internal Medicine School of Medicine Keio University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuka","family":"Namikawa","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Department of Internal Medicine School of Medicine Keio University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuyoshi","family":"Matsuoka","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Department of Internal Medicine School of Medicine Keio University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiro","family":"Sato","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Department of Internal Medicine School of Medicine Keio University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazutaka","family":"Koganei","sequence":"additional","affiliation":[{"name":"Department of Surgery Yokohama Municipal Citizen's Hospital Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Sugita","sequence":"additional","affiliation":[{"name":"Department of Surgery Yokohama Municipal Citizen's Hospital Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takanori","family":"Kanai","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Department of Internal Medicine School of Medicine Keio University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshifumi","family":"Hibi","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Department of Internal Medicine School of Medicine Keio University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,4,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2109"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1733"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200519229"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.10.6900"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0804012"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1511"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0804647"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/00042737-199709000-00013"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/00042737-199910000-00006"},{"key":"e_1_2_9_11_1","first-page":"2269","article-title":"Unique CD14+ intestinal macrophages contribute to the pathogenesis of Crohn disease via IL\u201023\/IFN\u2010\u03b3 axis","volume":"118","author":"Kamada N","year":"2008","journal-title":"J Clin Invest"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI30602"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2000.20260"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0804369"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2010.05.040"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.20934"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2012.03554.x"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M209706200"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(02)02550-0"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.1.06546"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21458"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23032"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04330"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2009.08.001"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840160317"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840100409"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2008.04.171"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2011.11.006"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0025637"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02982715"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm901434t"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2001.28021"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24525"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.12.021"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2009.08.001"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm7015864"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.20524"}],"container-title":["Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fimm.12045","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imm.12045","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/imm.12045","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imm.12045","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T05:40:56Z","timestamp":1698644456000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/imm.12045"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,4,8]]},"references-count":36,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2013,5]]}},"alternative-id":["10.1111\/imm.12045"],"URL":"https:\/\/doi.org\/10.1111\/imm.12045","archive":["Portico"],"relation":{},"ISSN":["0019-2805","1365-2567"],"issn-type":[{"value":"0019-2805","type":"print"},{"value":"1365-2567","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,4,8]]},"assertion":[{"value":"2012-07-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-11-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-04-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}