Clec4d, also known as CLECSF8 and MCL, is a member of the C-type lectin/C-type lectin-like domain superfamily. It functions as a pattern recognition receptor, playing a role in immunity. Clec4d is associated with signaling pathways such as NF-κB/AKT and is crucial for anti-mycobacterial immunity. Genetic models like KO mouse models are valuable for studying its functions [6,8].

In gastric cancer, high Clec4d expression promotes cell proliferation and migration via the NF-κB/AKT signaling pathways, and knockdown of Clec4d inhibits these cancer phenotypes [1]. In liver fibrosis, a subtype of splenic monocytes (sM-2s) highly expresses Clec4d, and these cells can activate hepatic stellate cells, exacerbating liver fibrosis [2]. In acute myocardial infarction, CLEC4D is significantly expressed in intermediate monocytes derived from patients without plaque rupture [3]. In addition, Clec4d may be involved in pathological cardiac remodeling as it is a target of HIPK2 [4]. In coronary artery disease progression in type 1 diabetes, CLEC4D was identified as a diagnostic biomarker [5]. In Gram-negative pneumonia, Clec4d -/- mice were highly susceptible with a progressive increase in bacterial burden and hyperinflammatory response, suggesting Clec4d plays a role in inflammation resolution [7].

In conclusion, Clec4d plays diverse roles in various biological processes and diseases. KO mouse models have revealed its importance in anti-mycobacterial immunity, inflammation resolution, and disease-related cell behaviors such as cancer cell proliferation and migration. Its functions span across multiple disease areas including cancer, liver fibrosis, myocardial infarction, and coronary artery disease, highlighting its significance in understanding disease mechanisms and potential therapeutic targets.

References:

1. Yang, Yang, Zhang, Mengmeng, Cai, Fenglin, Yin, Yiqing, Deng, Jingyu. 2024. CLEC4D as a Novel Prognostic Marker Boosts the Proliferation and Migration of Gastric Cancer via the NF-κB/AKT Signaling Pathway. In International journal of general medicine, 17, 1923-1935. doi:10.2147/IJGM.S458228. https://pubmed.ncbi.nlm.nih.gov/38736669/

2. Zhang, Shaoying, Wan, Dan, Zhu, Mengchen, Chen, Yongyan, Li, Zongfang. 2023. CD11b + CD43 hi Ly6C lo splenocyte-derived macrophages exacerbate liver fibrosis via spleen-liver axis. In Hepatology (Baltimore, Md.), 77, 1612-1629. doi:10.1002/hep.32782. https://pubmed.ncbi.nlm.nih.gov/36098707/

3. Qian, Jun, Gao, Yanhua, Lai, Yan, Chen, Fei, Liu, Xuebo. 2022. Single-Cell RNA Sequencing of Peripheral Blood Mononuclear Cells From Acute Myocardial Infarction. In Frontiers in immunology, 13, 908815. doi:10.3389/fimmu.2022.908815. https://pubmed.ncbi.nlm.nih.gov/35844519/

4. Zhou, Qiulian, Meng, Danni, Li, Feng, Sluijter, Joost P G, Xiao, Junjie. 2022. Inhibition of HIPK2 protects stress-induced pathological cardiac remodeling. In EBioMedicine, 85, 104274. doi:10.1016/j.ebiom.2022.104274. https://pubmed.ncbi.nlm.nih.gov/36182775/

5. Zhou, Yufei, Liu, Chunjiang, Zhang, Zhongzheng, Tong, Mingyue, Zhang, Gang. 2023. Identification and validation of diagnostic biomarkers of coronary artery disease progression in type 1 diabetes via integrated computational and bioinformatics strategies. In Computers in biology and medicine, 159, 106940. doi:10.1016/j.compbiomed.2023.106940. https://pubmed.ncbi.nlm.nih.gov/37075605/

6. Kerscher, Bernhard, Wilson, Gillian J, Reid, Delyth M, Willment, Janet A, Brown, Gordon D. 2015. Mycobacterial receptor, Clec4d (CLECSF8, MCL), is coregulated with Mincle and upregulated on mouse myeloid cells following microbial challenge. In European journal of immunology, 46, 381-9. doi:10.1002/eji.201545858. https://pubmed.ncbi.nlm.nih.gov/26558717/

7. Steichen, Anthony L, Binstock, Brandilyn J, Mishra, Bibhuti B, Sharma, Jyotika. 2013. C-type lectin receptor Clec4d plays a protective role in resolution of Gram-negative pneumonia. In Journal of leukocyte biology, 94, 393-8. doi:10.1189/jlb.1212622. https://pubmed.ncbi.nlm.nih.gov/23709686/

8. Wilson, Gillian J, Marakalala, Mohlopheni J, Hoving, Jennifer C, van Crevel, Reinout, Brown, Gordon D. . The C-type lectin receptor CLECSF8/CLEC4D is a key component of anti-mycobacterial immunity. In Cell host & microbe, 17, 252-9. doi:10.1016/j.chom.2015.01.004. https://pubmed.ncbi.nlm.nih.gov/25674984/