2. Academic Validation
  3. IFN-γ regulates the transformation of microglia into dendritic-like cells via the ERK/c-myc signaling pathway during cerebral ischemia/reperfusion in mice

IFN-γ regulates the transformation of microglia into dendritic-like cells via the ERK/c-myc signaling pathway during cerebral ischemia/reperfusion in mice

  • Neurochem Int. 2020 Dec;141:104860. doi: 10.1016/j.neuint.2020.104860.
Haiyu Zhang 1,  Tongshuai Zhang 2,  Dandan Wang 3,  Yixiang Jiang 4,  Tieyun Guo 5,  Yao Zhang 6,  Fan Zhu 7,  Kaiyu Han 8,  Lili Mu 9,  Guangyou Wang 10
Affiliations

Affiliations

  • 1 Department of Cardiology, The First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, China. Electronic address: [email protected].
  • 2 Department of Neurobiology, Harbin Medical University, Harbin, 150081, China. Electronic address: [email protected].
  • 3 Wu Lian De Memorial Hospital, The First Affiliated Hospital OfHarbin Medical University, Harbin, 150000, China. Electronic address: [email protected].
  • 4 Department of Neurobiology, Harbin Medical University, Harbin, 150081, China. Electronic address: [email protected].
  • 5 Department of Basic Medical, Harbin Medical University, Harbin, 150081, China. Electronic address: [email protected].
  • 6 Department of Neurobiology, Harbin Medical University, Harbin, 150081, China. Electronic address: [email protected].
  • 7 Department of Neurobiology, Harbin Medical University, Harbin, 150081, China. Electronic address: [email protected].
  • 8 Department of Respiratory and Critical Medicine, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China. Electronic address: [email protected].
  • 9 Department of Neurobiology, Harbin Medical University, Harbin, 150081, China. Electronic address: [email protected].
  • 10 Department of Neurobiology, Harbin Medical University, Harbin, 150081, China. Electronic address: [email protected].
PMID: 33022312 DOI: 10.1016/j.neuint.2020.104860
Abstract

Cerebral ischemia-reperfusion injury induces a secondary immune inflammatory reaction that exacerbates brain injury and clinical prognosis. Dendritic cells (DCs) and microglia are both important regulators of neuroinflammation. Studies have confirmed that a large number of cells express the DC surface marker CD11c in the ischemic area, and some of these cells also express microglial markers. However, the specific mechanism of transformation between microglia and DCs and their roles in the process of cerebral ischemia-reperfusion injury are still not clear. In this study, we established a mouse model and flow cytometry was used to detect the expression of mature DC surface molecules in activated microglia. IFN-γ knockout mice were used to determine the regulatory effect of IFN-γ on microglial transformation. We found that CD11c+ cells were derived from microglia after ischemia-reperfusion injury, and this group of cells highly expressed MHC-II molecules and other costimulatory molecules, such as CD80 and CD86, which were regulated by IFN-γ and its downstream signaling molecules ERK/c-Myc. In summary, our results showed in cerebral ischemia-reperfusion injury, IFN-γ regulates the transformation of microglia to DC-like cells. Microglial-derived DC-like cells possess the ability to present antigens and activate naïve T cells which is regulated by the ERK/c-Myc signaling pathway.

Keywords

Cerebral ischemia-reperfusion injury; Dentritic cells; ERK/C-myc; IFN-γ; Microglia.

Figures
Products