HMOC, a chrysin derivative, induces tolerogenic properties in lipopolysaccharide-stimulated dendritic cells

Abstract

Although we previously identified a new hydroxymethoxyl chrysin derivative (HMOC) using ionizing radiation, the anti-inflammatory mechanism of HMOC in dendritic cells remains unclear. In this study, we investigate the effects of HMOC on phenotypic and functional changes in activated bone marrow-derived dendritic cells (BMDCs). In lipopolysaccharide (LPS)-stimulated BMDCs, HMOC treatment inhibited pro-inflammatory cytokines (TNF-α, IL-12p70, and IL-1β), surface molecules (CD80, CD86, MHC-I, and MHC-II), and antigen-presentation to MHC-I and II without a decrease in IL-10. Furthermore, HMOC increased indoleamine 2,3-dioxygenase-1 (IDO1) activity via activation of JNK and p38 signaling in the presence of LPS. Interestingly, LPS-stimulated DCs treated with HMOC inhibited the proliferation and activation of CD4⁺ and CD8⁺ T cells, as well as differentiation of CD4⁺ T cells into Th1-, Th2- and Th17 cells. In addition, LPS-stimulated DCs treated with HMOC induced an increase in CD4⁺CD25⁺Foxp3⁺ regulatory T cells (Tregs). Collectively, our results suggest that HMOC confers tolerogenic properties in BMDCs, which are responsible for inducing Th cell differentiation to Tregs. Our findings provide a better understanding of the anti-inflammatory mechanism of HMOC in DCs and may contribute to development of a valuable therapeutic candidate for atopic dermatitis.

Keywords: 3-Dioxygenase; Chrysin derivative; Indoleamine 2; Regulatory T cells; Tolerogenic dendritic cells.