Induction of Th1-biased cytokine production by alpha-carba-GalCer, a neoglycolipid ligand for NKT cells.
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| Abstract |
NKT cells are characterized by their production of both T(h)1 and T(h)2 cytokines immediately after stimulation with alpha-galactosylceramide (alpha-GalCer), which is composed of alpha-galactopyranose linked to ceramide (itself composed of sphingosine and fatty-acyl chains); the chain length of the ceramide varies and this affects the ability of alpha-GalCer to stimulate cytokine production. However, the contribution of its galactopyranose sugar moiety remains unclear. We synthesized alpha-carba-GalCer, which has an alpha-linked carba-galactosyl moiety; here, the 5a'-oxygen atom of the D-galactopyranose ring of alpha-GalCer is replaced by a methylene group. The alpha-carba-GalCer was more stable and showed higher affinity to the NKT receptor. It thus enhanced and prolonged production of IL-12 and IFN-gamma compared with alpha-GalCer, resulting in augmented NKT cell-mediated adjuvant effects in vivo. The alpha-carba-GalCer, which has an ether linkage, was more resistant to degradation by liver microsomes than was alpha-GalCer, which has an acetal bond. Modulation of the sugar moiety in glycolipids might therefore provide optimal therapeutic reagents for protective immune responses against tumor or pathogens.
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| Authors | Takuya Tashiro, Etsuko Sekine-Kondo, Tomokuni Shigeura, Ryusuke Nakagawa, Sayo Inoue, Miyuki Omori-Miyake, Tomoki Chiba, Naomi Hongo, Shin-Ichiro Fujii, Kanako Shimizu, Yohei Yoshiga, Takayuki Sumida, Kenji Mori, Hiroshi Watarai, Masaru Taniguchi |
| Journal | International immunology (Int Immunol) Vol. 22 Issue 4 Pg. 319-28 (Apr 2010) ISSN: 1460-2377 [Electronic] England |
| PMID | 20181652 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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