Immunomodulatory effects of D-allose on cytokine production by plasmacytoid dendritic cells.

D-Allose is classified as a 'rare sugar,' i.e., part of the group of monosaccharides that are present in low quantities in the natural world. D-Allose has been demonstrated to exert many physiological functions. The effects of the rare sugars on immune responses are largely unexplored. Here, we investigated the physiological effects of D-allose on murine dendritic cells' cytokine production. When plasmacytoid dendritic cells (pDCs) were stimulated with a Toll-like receptor 7 (TLR7) ligand, a single-stranded RNA (ssRNA), or a TLR9 ligand, CpG DNA, in the medium containing D-allose, the productions of both interferon-alpha (IFN-α) and interleukin (IL)-12p40 were severely decreased. In contrast, a normal production of these cytokines was observed when pDCs were stimulated with other TLR7 ligands, an imidazoquinoline, or a guanosine analog. In contrast to the pDCs, conventional dendritic cells (cDCs) produced IL-12p40 and tumor necrosis factor-alpha (TNF-α) in response to an imidazoquinoline or CpG DNA even though D-allose was present in the medium. D-Allose did not induce pDC death, and not inhibit the endocytic uptake of fluorophore-labeled CpG DNA into pDCs. These results suggested that D-allose exerts its inhibitory effects after CpG DNA is internalized. We analyzed the TLR7/9 signal-induced activation of downstream signaling molecules in pDCs and observed that when pDCs were stimulated with a ssRNA or CpG DNA, the phosphorylation status of the MAPK family, which includes Erk1/2, JNK/SAPK, and p38 MAPK, was attenuated in the presence of D-allose compared to D-glucose controls. The stimulation of pDCs with an imidazoquinoline induced a strong phosphorylation of these MAPK family members even in the presence of D-allose. These findings reveal that D-allose can inhibit the cytokine production by pDCs stimulated with ssRNA or CpG DNA via an attenuation of the phosphorylation of MAPK family members.

The mechanism of action of Spi-B in the transcriptional activation of the interferon-α4 gene.

Plasmacytoid dendritic cells (pDCs) are characterized by an exclusive expression of nucleic acid sensing Toll-like receptor 7 (TLR7) and TLR9, and production of high amounts of type I interferon (IFN) in response to TLR7/9 signaling. This function is crucial for both antiviral immunity and the pathogenesis of autoimmune diseases. An Ets family transcription factor, i.e., Spi-B (which is highly expressed in pDCs) is required for TLR7/9 signal-induced type I IFN production and can transactivate IFN-α promoter in synergy with IFN regulatory factor-7 (IRF-7). Herein, we analyzed how Spi-B contributes to the transactivation of the Ifna4 promoter. We performed deletion and/or mutational analyses of the Ifna4 promoter and an electrophoretic mobility shift assay (EMSA) and observed an Spi-B binding site in close proximity to the IRF-7 binding site. The EMSA results also showed that the binding of Spi-B to the double-stranded DNA probe potentiated the recruitment of IRF-7 to its binding site. We also observed that the association of Spi-B with transcriptional coactivator p300 was required for the Spi-B-induced synergistic enhancement of the Ifna4 promoter activity by Spi-B. These results clarify the molecular mechanism of action of Spi-B in the transcriptional activation of the Ifna4 promoter.

Li local configurations for the trimerized state of the geometrically frustrated triangular lattice system Li(1-x)V O2 with 0 ≤ x ≤ 0.14.

The Li de-intercalation effects for the trimerized state of the geometrically frustrated triangular lattice LiV O(2) are investigated through measurements of x-ray diffraction, magnetic susceptibility and magic-angle spinning-nuclear magnetic resonance (MAS-NMR). Li(1-x)V O(2) with 0 ≤ x ≤ 0.14 obtained with a soft-chemistry synthesis is a single phase. All of the data are understood by considering that the partial substitution for V(3+) (spin-1) with V(4+) (spin-½) leads to the coexistence of the spin-singlet and spin-½ trimers.