Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 20 August 2018 / Approved: 20 August 2018 / Online: 20 August 2018 (12:58:07 CEST)

A peer-reviewed article of this Preprint also exists.

Jeon, J.H.; Lee, B.-C.; Kim, D.; Cho, D.; Kim, T.S. Hydrophilic Astragalin Galactoside Induces T Helper Type 1-Mediated Immune Responses via Dendritic Cells. Int. J. Mol. Sci. 2018, 19, 3120. Jeon, J.H.; Lee, B.-C.; Kim, D.; Cho, D.; Kim, T.S. Hydrophilic Astragalin Galactoside Induces T Helper Type 1-Mediated Immune Responses via Dendritic Cells. Int. J. Mol. Sci. 2018, 19, 3120.

Abstract

A flavonoid Astragalin (kaempferol-3-O-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-O- β-D-isomaltotrioside, Ast-Gal) on dendritic cell (DC) maturation and T helper (Th) cell-mediated immune responses. Ast-Gal significantly increased maturation and activation of DCs through up-regulation of surface markers, such as CD80, CD86, and MHC II in a dose-dependent manner, while Ast had little effects. Also, Ast-Gal-treated DCs markedly secreted immune-stimulating cytokines such as 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 mAb to cultures of Ast-Gal-treated DCs and CD4+ T cells significantly increased 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.

Keywords

Astragalin galactoside, hydrophilic modification, Th1 cell, Dendritic cell, adjuvant

Subject

Biology and Life Sciences, Immunology and Microbiology

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