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Articles by R Nakagawa
Total Records ( 2 ) for R Nakagawa
  K Ichiyama , M Hashimoto , T Sekiya , R Nakagawa , Y Wakabayashi , Y Sugiyama , K Komai , I Saba , T Moroy and A. Yoshimura

Th cells have long been divided into two subsets, Th1 and Th2; however, recently, Th17 and inducible regulatory T (iTreg) cells were identified as new Th cell subsets. Although Th1- and Th2-polarizing cytokines have been shown to suppress Th17 and iTreg development, transcriptional regulation of Th17 and iTreg differentiation by cytokines remains to be clarified. In this study, we found that expression of the growth factor independent 1 (Gfi1) gene, which has been implicated in Th2 development, was repressed in Th17 and iTreg cells compared with Th1 and Th2 lineages. Gfi1 expression was enhanced by the IFN-/STAT1 and IL-4/STAT6 pathways, whereas it was repressed by the transforming growth factor-β1 stimulation at the promoter level. Over-expression of Gfi1 strongly reduced IL-17A transcription in the EL4 T cell line, as well as in primary T cells. This was due to the blockade of recruitment of retinoid-related orphan receptor t to the IL-17A promoter. In contrast, IL-17A expression was significantly enhanced in Gfi1-deficient T cells under Th17-promoting differentiation conditions as compared with wild-type T cells. In contrast, the impacts of Gfi1 in iTregs were not as strong as in Th17 cells. Taken together, these data strongly suggest that Gfi1 is a negative regulator of Th17 differentiation, which represents a novel mechanism for the regulation of Th17 development by cytokines.

  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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