Clec4a2, also known as dendritic cell immunoreceptor (DCIR), is a member of the C-type lectin receptor family. It plays important roles in the homeostasis of the immune and bone systems, and is involved in regulating macrophage polarization, tissue adaptation of macrophages, and immune-related signaling pathways [1,2,3]. Genetic models, such as KO/CKO mouse models, have been crucial in studying its functions.

In a LysMCre+ Clec4a2flox/DTR mouse strain, Clec4a2 deficiency led to the loss of resident vascular macrophages and their homeostatic properties, causing dysfunctional cholesterol metabolism, enhanced toll-like receptor triggering, and exacerbating atherosclerosis [1]. In Clec4a2-/- mice, dextran sodium sulfate (DSS)-induced colitis and azoxymethane-DSS-induced intestinal tumors were reduced, with enhanced STAT5 phosphorylation and expression of Csf2 and tight junction genes [3]. In aged Dcir-/- (Clec4a2 knockout) mice, they spontaneously developed sialadenitis and enthesitis associated with elevated serum autoantibodies, and showed an exacerbated response to collagen-induced arthritis due to excessive expansion of the DC population [4].

In conclusion, Clec4a2 is essential for maintaining macrophage homeostasis, regulating immune responses, and preventing certain diseases. The use of KO/CKO mouse models has revealed its role in diseases such as atherosclerosis, colitis, and autoimmune diseases, providing important insights into the underlying mechanisms and potential therapeutic targets for these conditions.

References:

1. Park, Inhye, Goddard, Michael E, Cole, Jennifer E, Drozdov, Ignat, Monaco, Claudia. 2022. C-type lectin receptor CLEC4A2 promotes tissue adaptation of macrophages and protects against atherosclerosis. In Nature communications, 13, 215. doi:10.1038/s41467-021-27862-9. https://pubmed.ncbi.nlm.nih.gov/35017526/

2. Liao, Yilin, Yan, Qi, Cheng, Tiange, Ji, Yaoting, Shi, Bin. 2023. Sulforaphene Inhibits Periodontitis through Regulating Macrophage Polarization via Upregulating Dendritic Cell Immunoreceptor. In Journal of agricultural and food chemistry, 71, 15538-15552. doi:10.1021/acs.jafc.3c02619. https://pubmed.ncbi.nlm.nih.gov/37823224/

3. Sun, Haiyang, Tang, Ce, Chung, Soo-Hyun, Asano, Masahide, Iwakura, Yoichiro. . Blocking DCIR mitigates colitis and prevents colorectal tumors by enhancing the GM-CSF-STAT5 pathway. In Cell reports, 40, 111158. doi:10.1016/j.celrep.2022.111158. https://pubmed.ncbi.nlm.nih.gov/35926458/

4. Fujikado, Noriyuki, Saijo, Shinobu, Yonezawa, Tomo, Nose, Masato, Iwakura, Yoichiro. 2008. Dcir deficiency causes development of autoimmune diseases in mice due to excess expansion of dendritic cells. In Nature medicine, 14, 176-80. doi:10.1038/nm1697. https://pubmed.ncbi.nlm.nih.gov/18204462/