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

Kenjiro Takao; Makiko Suzuki; Ryo Miyazaki; Minoru Miyake; Kazuya Akimitsu; Katsuaki Hoshino

doi:10.1016/j.bbrc.2022.08.037

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

Biochem Biophys Res Commun. 2022 Oct 30:627:130-136. doi: 10.1016/j.bbrc.2022.08.037. Epub 2022 Aug 17.

Authors

Kenjiro Takao¹, Makiko Suzuki², Ryo Miyazaki³, Minoru Miyake³, Kazuya Akimitsu⁴, Katsuaki Hoshino⁵

Affiliations

¹ Department of Immunology, Faculty of Medicine, Kagawa University, Miki, Kagawa, 761-0793, Japan; Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Kagawa University, Miki, Kagawa, 761-0793, Japan.
² Department of Immunology, Faculty of Medicine, Kagawa University, Miki, Kagawa, 761-0793, Japan.
³ Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Kagawa University, Miki, Kagawa, 761-0793, Japan.
⁴ International Institute of Rare Sugar Research and Education, Kagawa University, Miki, Kagawa, 761-0795, Japan.
⁵ Department of Immunology, Faculty of Medicine, Kagawa University, Miki, Kagawa, 761-0793, Japan; International Institute of Rare Sugar Research and Education, Kagawa University, Miki, Kagawa, 761-0795, Japan. Electronic address: hoshino.katsuaki@kagawa-u.ac.jp.

PMID: 36030654
DOI: 10.1016/j.bbrc.2022.08.037

Abstract

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.

Keywords: D-allose; Interferon-α; MAPK; Plasmacytoid dendritic cell; Rare sugar.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cytokines
DNA
Dendritic Cells
Glucose / pharmacology
Immunity
Ligands
Mice
Toll-Like Receptor 7*
Toll-Like Receptor 9*

Substances

Cytokines
Ligands
Toll-Like Receptor 7
Toll-Like Receptor 9
allose
DNA
Glucose