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

Ha Yeon Song, Woo Sik Kim, Jeong Moo Han, Woo Yong Park, Seung Taik Lim, Eui Baek Byun

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number107523
JournalInternational Immunopharmacology
Volume95
DOIs
Publication statusPublished - 2021 Jun

Keywords

  • 3-Dioxygenase
  • Chrysin derivative
  • Indoleamine 2
  • Regulatory T cells
  • Tolerogenic dendritic cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

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