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The complexes between CD1d and ligands activate natural killer T cells by T cell receptor recognition, leading to the secretion of various cytokines (IFN-\u03b3, IL-4, IL-17A, etc.). Herein, we report structure\u2013activity relationship studies of \u03b1-GalCer derivatives containing various functional groups in their lipid acyl chains. Several derivatives have been identified as potent CD1d ligands displaying higher cytokine induction levels and\/or unique cytokine polarization. The studies also indicated that flexibility of the lipid moiety can affect the binding affinity, the total cytokine production level and\/or cytokine biasing. Based on our immunological evaluation and investigation of physicochemical properties, we chose bisamide- and Bz amide-containing derivatives\n                    <jats:bold>2<\/jats:bold>\n                    and\n                    <jats:bold>3<\/jats:bold>\n                    , and evaluated their in vivo efficacy in a DSS-induced model of ulcerative colitis. The derivative\n                    <jats:bold>3<\/jats:bold>\n                    that exhibits Th2- and Th17-biasing responses, demonstrated significant protective effects against intestinal inflammation in the DSS-induced model, after a single intraperitoneal injection.\n                  <\/jats:p>","DOI":"10.1038\/s41598-020-72280-4","type":"journal-article","created":{"date-parts":[[2020,9,25]],"date-time":"2020-09-25T06:02:43Z","timestamp":1601013763000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Polar functional group-containing glycolipid CD1d ligands modulate cytokine-biasing responses and prevent experimental colitis"],"prefix":"10.1038","volume":"10","author":[{"given":"Shinsuke","family":"Inuki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natsumi","family":"Hirata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emi","family":"Kashiwabara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junichiro","family":"Kishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiko","family":"Aiba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiaki","family":"Teratani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wataru","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshimi","family":"Kojima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Maruyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takanori","family":"Kanai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukari","family":"Fujimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,9,25]]},"reference":[{"issue":"2","key":"72280_CR1","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1038\/nri3369","volume":"13","author":"PJ Brennan","year":"2013","unstructured":"Brennan, P. 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Other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"15766"}}