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Articles by T Tashiro
Total Records ( 3 ) for T Tashiro
  M Taniguchi , T Tashiro , N Dashtsoodol , N Hongo and H. Watarai
 

Invariant NKT (iNKT) cells bridge innate and acquired immunity and play an important role in both protective and regulatory responses. The nature of the response is dictated by the initial cytokine environment: interaction with IL-10-producing cells induces negative regulatory Th2/regulatory T cell-type iNKT cells, while that with IL-12-producing cells results in pro-inflammatory Th1-type responses. Particularly, in the anti-tumor response, iNKT cells mediate adjuvant activity by their production of IFN-, which in turn activates both innate and acquired immune systems. Thus, upon activation of iNKT cells, both MHC and MHC+ tumor cells can be efficiently eliminated. On the basis of these mechanisms, iNKT cell-targeted adjuvant cell therapies have been developed and have shown great promise in initial clinical trials on cancer patients.

  T Tashiro , E Sekine Kondo , T Shigeura , R Nakagawa , S Inoue , M Omori Miyake , T Chiba , N Hongo , S. i Fujii , K Shimizu , Y Yoshiga , T Sumida , K Mori , H Watarai and M. Taniguchi
 

NKT cells are characterized by their production of both Th1 and Th2 cytokines immediately after stimulation with -galactosylceramide (-GalCer), which is composed of -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 -GalCer to stimulate cytokine production. However, the contribution of its galactopyranose sugar moiety remains unclear. We synthesized -carba-GalCer, which has an -linked carba-galactosyl moiety; here, the 5a'-oxygen atom of the D-galactopyranose ring of -GalCer is replaced by a methylene group. The -carba-GalCer was more stable and showed higher affinity to the NKT receptor. It thus enhanced and prolonged production of IL-12 and IFN- compared with -GalCer, resulting in augmented NKT cell-mediated adjuvant effects in vivo. The -carba-GalCer, which has an ether linkage, was more resistant to degradation by liver microsomes than was -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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