Induction of Th1-biased cytokine production by α-carba-GalCer, a neoglycolipid ligand for NKT cells

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

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)319-328
Number of pages10
JournalInternational Immunology
Volume22
Issue number4
DOIs
Publication statusPublished - 2010 Feb 24
Externally publishedYes

Fingerprint

Natural Killer T-Cells
Galactose
Ceramides
Cytokines
Ligands
Galactosylceramides
Acetals
Sphingosine
Glycolipids
Liver Microsomes
Interleukin-12
Ether
Oxygen
Neoplasms
Therapeutics

Keywords

  • CD1d
  • Glycolipid
  • IFN-γ
  • NKT cells
  • TCR

ASJC Scopus subject areas

  • Immunology

Cite this

Tashiro, T., Sekine-Kondo, E., Shigeura, T., Nakagawa, R., Inoue, S., Omori-Miyake, M., ... Taniguchi, M. (2010). Induction of Th1-biased cytokine production by α-carba-GalCer, a neoglycolipid ligand for NKT cells. International Immunology, 22(4), 319-328. https://doi.org/10.1093/intimm/dxq012

Induction of Th1-biased cytokine production by α-carba-GalCer, a neoglycolipid ligand for NKT cells. / Tashiro, Takuya; Sekine-Kondo, Etsuko; Shigeura, Tomokuni; Nakagawa, Ryusuke; Inoue, Sayo; Omori-Miyake, Miyuki; Chiba, Tomoki; Hongo, Naomi; Fujii, Shin Ichiro; Shimizu, Kanako; Yoshiga, Yohei; Sumida, Takayuki; Mori, Kenji; Watarai, Hiroshi; Taniguchi, Masaru.

In: International Immunology, Vol. 22, No. 4, 24.02.2010, p. 319-328.

Research output: Contribution to journalArticle

Tashiro, T, Sekine-Kondo, E, Shigeura, T, Nakagawa, R, Inoue, S, Omori-Miyake, M, Chiba, T, Hongo, N, Fujii, SI, Shimizu, K, Yoshiga, Y, Sumida, T, Mori, K, Watarai, H & Taniguchi, M 2010, 'Induction of Th1-biased cytokine production by α-carba-GalCer, a neoglycolipid ligand for NKT cells', International Immunology, vol. 22, no. 4, pp. 319-328. https://doi.org/10.1093/intimm/dxq012
Tashiro T, Sekine-Kondo E, Shigeura T, Nakagawa R, Inoue S, Omori-Miyake M et al. Induction of Th1-biased cytokine production by α-carba-GalCer, a neoglycolipid ligand for NKT cells. International Immunology. 2010 Feb 24;22(4):319-328. https://doi.org/10.1093/intimm/dxq012
Tashiro, Takuya ; Sekine-Kondo, Etsuko ; Shigeura, Tomokuni ; Nakagawa, Ryusuke ; Inoue, Sayo ; Omori-Miyake, Miyuki ; Chiba, Tomoki ; Hongo, Naomi ; Fujii, Shin Ichiro ; Shimizu, Kanako ; Yoshiga, Yohei ; Sumida, Takayuki ; Mori, Kenji ; Watarai, Hiroshi ; Taniguchi, Masaru. / Induction of Th1-biased cytokine production by α-carba-GalCer, a neoglycolipid ligand for NKT cells. In: International Immunology. 2010 ; Vol. 22, No. 4. pp. 319-328.
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