Hydrophilic Astragalin Galactoside Induces T Helper Type 1-Mediated Immune Responses via Dendritic Cells

• Published in: International journal of molecular sciences Vol. 19; no. 10; p. 3120
• Main Authors: Jeon, Jae Hyoung, Lee, Byung-Cheol, Kim, Doman, Cho, Daeho, Kim, Tae Sung
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 11.10.2018; MDPI AG
• Subjects: adjuvant; Animals; Antigen Presentation - immunology; Antigen-Presenting Cells - drug effects; Antigen-Presenting Cells - immunology; Antigen-Presenting Cells - metabolism; astragalin galactoside; Biomarkers; Cytokines - genetics; Cytokines - metabolism; dendritic cell; Dendritic Cells - immunology; Dendritic Cells - metabolism; Galactosides - pharmacology; Gene Expression; hydrophilic modification; Immunity - drug effects; Immunophenotyping; Kaempferols - pharmacology; Mice; T-Lymphocyte Subsets - drug effects; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Th1 cell; Th1 Cells - drug effects; Th1 Cells - immunology; Th1 Cells - metabolism; hydrophilic modification; Th1 cell; adjuvant; astragalin galactoside; dendritic cell
• ISSN: 1422-0067; 1422-0067
• DOI: 10.3390/ijms19103120

A flavonoid Astragalin (kaempferol-3- -β-d-glucopyranoside, Ast) has several biological activities including anti-oxidant, anti-HIV, and anti-allergic effects. Nonetheless, its insolubility in hydrophilic solvents imposes restrictions on its therapeutic applications. In this study, we investigated the effects of water-soluble astragalin-galactoside (kaempferol-3- -β-d-isomaltotrioside, Ast-Gal) on murine bone marrow-derived dendritic cell (DC) maturation and T helper (Th) cell-mediated immune responses. Ast-Gal significantly increased maturation and activation of DCs through the upregulation of surface markers, such as cluster of differentiation (CD)80, CD86, and Major histocompatibility complex (MHC) II in a dose-dependent manner, while Ast had little effects. Additionally, Ast-Gal-treated DCs markedly secreted immune-stimulating cytokines such as interleukin (IL)-1β, IL-6, and IL-12. Importantly, Ast-Gal strongly increased expression of IL-12, a polarizing cytokine of Th1 cells. In a co-culture system of DCs and CD4⁺ T cells, Ast-Gal-treated DCs preferentially differentiates naïve CD4⁺ T cells into Th1 cells. The addition of neutralizing IL-12 monoclonal antibody (mAb) to cultures of Ast-Gal-treated DCs and CD4⁺ T cells significantly decreased interferon (IFN)-γ production, thereby indicating that Ast-Gal-stimulated DCs enhance the Th1 response through IL-12 production by DCs. Injection with Ast-Gal-treated DCs in mice increased IFN-γ-secreting Th1 cell population. Collectively, these findings indicate that hydrophilically modified astragalin can enhance Th1-mediated immune responses via DCs and point to a possible application of water-soluble astragalin-galactoside as an immune adjuvant.