Dectin-1 stimulates IL-33 expression in dendritic cells via upregulation of IRF4

  • Lab Invest. 2018 Jun;98(6):708-714. doi: 10.1038/s41374-018-0047-2.
Dongjiao Wang  1 ,  Sujun Gao  2 ,  Jintong Chen  3 ,  Yinghua Zhao  3 ,  Yuxue Jiang  3 ,  Xiao Chu  3 ,  Xiaohua Wang  4 ,  Ning Liu  1 ,  Tianxue Qin  2 ,  Qing Yi  3  5 ,  Ying Yue  6 ,  Siqing Wang  7
Affiliations
  • 1. Department of Gynecological Oncology, The First Hospital of Jilin University, Changchun, 130061, China.
  • 2. Department of Hematology, The First Hospital of Jilin University, Changchun, 130061, China.
  • 3. Department of Cancer Immunology, The First Hospital of Jilin University, Changchun, 130061, China.
  • 4. Department of Internal Medicine, Linhai First People's Hospital, Linhai, Zhejiang, 317000, China.
  • 5. Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, 44195, USA.
  • 6. Department of Gynecological Oncology, The First Hospital of Jilin University, Changchun, 130061, China. [email protected].
  • 7. Department of Cancer Immunology, The First Hospital of Jilin University, Changchun, 130061, China. [email protected].
PMID: 29540860 DOI: 10.1038/s41374-018-0047-2
Abstract

Interleukin-33 (IL-33) is a potent contributor to Antiviral immune responses and antitumor immunity. We recently discovered that IL-33 is overexpressed in dectin-1-activated dendritic cells (DCs). However, mechanisms of dectin-1-induced IL-33 expression in DCs remain elusive. Curdlan, an agonist of Dectin-1, was used to mature DCs in this study. We found that dectin-1-induced IL-33 expression in DCs relies on Syk and Raf-1 pathways. By using nuclear factor (NF)-κB inhibitors, we also found that dectin-1-induced IL-33 expression relies on NF-κB signaling. Furthermore, through Syk/Raf-1-NF-κB pathway, Dectin-1 signaling stimulates DCs to overexpress interferon regulatory factor 4 (IRF4), which directly upregulates the expression of IL-33 in dectin-1-activated DCs. Thus, our study provides new insights into the mechanisms of dectin-1-induced IL-33 expression in DCs and may provide new targets for improving DC-based Cancer Immunotherapy.

Products