Clec4f, encoding a C-type lectin receptor, is specifically expressed by Kupffer cells in mice [1,2,3,4,5,6,7,8]. It recognizes desialylated glycans and is involved in multiple biological processes. CLEC4F is important for the destruction of desialylated platelets in mice, which provides insights into the pathogenesis of thrombocytopenia in diseases like sepsis [1].

Using Clec4f -deficient (Clec4f-/-) mice, it was found that CLEC4F on Kupffer cells mediates the destruction of desialylated platelets in the liver in vivo, with desialylated platelets phagocytized by Kupffer cells in a CLEC4F -dependent manner [1]. In another study, Clec4f -cre mice were used to target Kupffer cells. Loss of the transcription factor ZEB2 in these macrophages led to their disappearance from tissues, suggesting ZEB2's role in maintaining macrophage tissue-specific identities, regulated in Kupffer cells by CLEC4F-mediated control of LXRα expression [2]. Also, in the context of hepatocellular carcinoma, Xdhf/fClec4fcre mice were used to study the role of XOR in Kupffer cells, revealing that XOR loss in monocyte-derived TAMs rather than Kupffer cells promoted M2 polarization and CD8+ T-cell exhaustion, exacerbating HCC progression [3].

In conclusion, Clec4f plays a crucial role in Kupffer-cell-mediated functions such as platelet destruction and maintaining macrophage identity. The use of Clec4f-deficient and Clec4f-cre mouse models has significantly advanced our understanding of these processes, with implications for diseases like thrombocytopenia in sepsis and hepatocellular carcinoma [1,2,3].