Development of monosaccharides that regulate the functions of the plasmacytoid dendritic cells.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08458
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Kagawa University
• Principal Investigator: Hoshino Katsuaki 香川大学, 医学部, 教授 (50324843)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 希少糖 / 形質細胞様樹状細胞 / サイトカイン / 自己免疫疾患 / 単糖 / 糖代謝

Outline of Final Research Achievements

The rare sugar D-allose, a C-3 epimer of D-glucose, was found to inhibit the function of plasmacytoid dendritic cells (pDCs), which are primarily responsible for the production of cytokines such as IFN-α and IL-12p40. We investigated the inhibitory mechanism of D-allose and found that activation of intracellular signaling molecules and glycolytic pathway were downregulated. In addition, treatment of R848-induced SLE model mice with D-allose tended to reduce the titer of anti-double-stranded DNA antibodies in serum. These results suggest that D-allose may have a protective effect against the pathogenesis of the SLE model by suppressing pDC function.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

免疫細胞に対する希少糖D-アロースの作用を初めて報告した。D-アロースは、形質細胞様樹状細胞のサイトカイン産生を著しく抑制する効果を有する。全身性エリテマトーデスに代表される自己免疫疾患では、形質細胞様樹状細胞によるインターフェロン-α産生の亢進が病態を悪化させる一因となっている。D-アロース標品の使用、および作用メカニズムの解明は、形質細胞様樹状細胞を標的とする新しい治療手段の開発に貢献すると考える。