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
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DOI：
10.1038/s41590-023-01634-7
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发表时间：
2023-10
影响因子：
30.5
通讯作者：
Jie Li;Xiao-Gang Liu;Rui-Liang Ge;Yu-Peng Yin;Yong-da Liu;Wan-Peng Lu;Mei Huang;Xue-Ying He;Jinghan Wang;Guoxiang Cai;Shu-han Sun;Ji-hang Yuan
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文献类型：
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作者：
Jie Li;Xiao-Gang Liu;Rui-Liang Ge;Yu-Peng Yin;Yong-da Liu;Wan-Peng Lu;Mei Huang;Xue-Ying He;Jinghan Wang;Guoxiang Cai;Shu-han Sun;Ji-hang Yuan
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.
