2. Academic Validation
  3. The ligation between ERMAP, galectin-9 and dectin-2 promotes Kupffer cell phagocytosis and antitumor immunity

The ligation between ERMAP, galectin-9 and dectin-2 promotes Kupffer cell phagocytosis and antitumor immunity

  • Nat Immunol. 2023 Oct 9. doi: 10.1038/s41590-023-01634-7.
Jie Li # 1,  Xiao-Gang Liu # 2,  Rui-Liang Ge # 3,  Yu-Peng Yin 1,  Yong-da Liu 1,  Wan-Peng Lu 1,  Mei Huang 1,  Xue-Ying He 1,  Jinghan Wang 4,  Guoxiang Cai 5 6,  Shu-Han Sun 7,  Ji-Hang Yuan 8 9
Affiliations

Affiliations

  • 1 Department of Medical Genetics, Shanghai Key Laboratory of Medical Bioprotection, Key Laboratory of Biological Defense, Ministry of Education, Naval Medical University, Shanghai, China.
  • 2 Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China.
  • 3 Department of Biliary Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China.
  • 4 Department of Hepatobiliary and Pancreatic Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
  • 5 Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. [email protected].
  • 6 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. [email protected].
  • 7 Department of Medical Genetics, Shanghai Key Laboratory of Medical Bioprotection, Key Laboratory of Biological Defense, Ministry of Education, Naval Medical University, Shanghai, China. [email protected].
  • 8 Department of Medical Genetics, Shanghai Key Laboratory of Medical Bioprotection, Key Laboratory of Biological Defense, Ministry of Education, Naval Medical University, Shanghai, China. [email protected].
  • 9 Shanghai Key Laboratory of Cell Engineering, Shanghai, China. [email protected].
  • # Contributed equally.
PMID: 37813965 DOI: 10.1038/s41590-023-01634-7
Abstract

Kupffer cells, the liver tissue resident macrophages, are critical in the detection and clearance of Cancer cells. However, the molecular mechanisms underlying their detection and phagocytosis of Cancer cells are still unclear. Using in vivo genome-wide CRISPR-Cas9 knockout screening, we found that the cell-surface transmembrane protein ERMAP expressed on various Cancer cells signaled to activate phagocytosis in Kupffer cells and to control of liver metastasis. ERMAP interacted with β-galactoside binding lectin Galectin-9 expressed on the surface of Kupffer cells in a manner dependent on glycosylation. Galectin-9 formed a bridging complex with ERMAP and the transmembrane receptor dectin-2, expressed on Kupffer cells, to induce the detection and phagocytosis of Cancer cells by Kupffer cells. Patients with low expression of ERMAP on tumors had more liver metastases. Thus, our study identified the ERMAP-galectin-9-dectin-2 axis as an 'eat me' signal for Kupffer cells.

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