TY - JOUR
T1 - Induction of Th1-biased cytokine production by α-carba-GalCer, a neoglycolipid ligand for NKT cells
AU - Tashiro, Takuya
AU - Sekine-Kondo, Etsuko
AU - Shigeura, Tomokuni
AU - Nakagawa, Ryusuke
AU - Inoue, Sayo
AU - Omori-Miyake, Miyuki
AU - Chiba, Tomoki
AU - Hongo, Naomi
AU - Fujii, Shin Ichiro
AU - Shimizu, Kanako
AU - Yoshiga, Yohei
AU - Sumida, Takayuki
AU - Mori, Kenji
AU - Watarai, Hiroshi
AU - Taniguchi, Masaru
N1 - Funding Information:
Grant-in-Aid for Young Scientists (B) (20790108) from the Ministry of Education, Culture, Sports, Science and Technology, Japan, to T.T.
PY - 2010/2/24
Y1 - 2010/2/24
N2 - NKT cells are characterized by their production of both Th1 and Th2 cytokines immediately after stimulation with α-galactosylceramide (α-GalCer), which is composed of α-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 α-GalCer to stimulate cytokine production. However, the contribution of its galactopyranose sugar moiety remains unclear. We synthesized α-carba-GalCer, which has an α-linked carba-galactosyl moiety; here, the 5a′-oxygen atom of the D-galactopyranose ring of α-GalCer is replaced by a methylene group. The α-carba-GalCer was more stable and showed higher affinity to the NKT receptor. It thus enhanced and prolonged production of IL-12 and IFN-γ compared with α-GalCer, resulting in augmented NKT cell-mediated adjuvant effects in vivo. The α-carba-GalCer, which has an ether linkage, was more resistant to degradation by liver microsomes than was α-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.
AB - NKT cells are characterized by their production of both Th1 and Th2 cytokines immediately after stimulation with α-galactosylceramide (α-GalCer), which is composed of α-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 α-GalCer to stimulate cytokine production. However, the contribution of its galactopyranose sugar moiety remains unclear. We synthesized α-carba-GalCer, which has an α-linked carba-galactosyl moiety; here, the 5a′-oxygen atom of the D-galactopyranose ring of α-GalCer is replaced by a methylene group. The α-carba-GalCer was more stable and showed higher affinity to the NKT receptor. It thus enhanced and prolonged production of IL-12 and IFN-γ compared with α-GalCer, resulting in augmented NKT cell-mediated adjuvant effects in vivo. The α-carba-GalCer, which has an ether linkage, was more resistant to degradation by liver microsomes than was α-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.
KW - CD1d
KW - Glycolipid
KW - IFN-γ
KW - NKT cells
KW - TCR
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U2 - 10.1093/intimm/dxq012
DO - 10.1093/intimm/dxq012
M3 - Article
C2 - 20181652
AN - SCOPUS:77954045916
VL - 22
SP - 319
EP - 328
JO - International Immunology
JF - International Immunology
SN - 0953-8178
IS - 4
ER -