Ccr9, short for C-C chemokine receptor 9, is a G protein-coupled receptor. It is expressed on several immune cells like dendritic cells, CD4+ T cells, and B cells, and its main function is to drive immune cell migration towards gradients of its cognate ligand CCL25 [3]. CCL25 is mostly produced by gut and thymic epithelial cells, and Ccr9 is thus implicated in gut-and thymus-related immune regulation [3]. Ccr9 is involved in various biological processes, such as inflammation and immune response, and is associated with diseases including cancer, inflammatory bowel disease, and cardiovascular disease [1,2,5].

Early research using Ccr9-deficient mouse models confirmed its physiological functions in inflammatory responses [2]. In adriamycin-induced cardiomyopathy, Ccr9 overexpression in mouse models aggravated cardiac dysfunction, while Ccr9 knockdown reversed the harmful effects of adriamycin, suggesting its role in this type of heart failure [6]. In the context of cancer, studies have shown that Ccr9 is overexpressed in a variety of malignant tumors, and its activation by CCL25 can interact with signaling pathways related to tumor chemoresistance and metastasis, as demonstrated in various research models [1,4].

In conclusion, Ccr9 plays essential roles in inflammation, immunity, and disease development. Model-based research, especially Ccr9-deficient mouse models, has revealed its functions in diseases such as inflammatory bowel disease, cardiovascular disease, and cancer, providing insights into potential therapeutic targets for these conditions.

References:

1. Xu, Baoping, Deng, Chao, Wu, Xue, Yang, Zhi, Yang, Yang. 2020. CCR9 and CCL25: A review of their roles in tumor promotion. In Journal of cellular physiology, 235, 9121-9132. doi:10.1002/jcp.29782. https://pubmed.ncbi.nlm.nih.gov/32401349/

2. Wu, Xue, Sun, Meng, Yang, Zhi, Liu, Yonglin, Yang, Yang. 2021. The Roles of CCR9/CCL25 in Inflammation and Inflammation-Associated Diseases. In Frontiers in cell and developmental biology, 9, 686548. doi:10.3389/fcell.2021.686548. https://pubmed.ncbi.nlm.nih.gov/34490243/

3. Pathak, Manisha, Lal, Girdhari. 2020. The Regulatory Function of CCR9+ Dendritic Cells in Inflammation and Autoimmunity. In Frontiers in immunology, 11, 536326. doi:10.3389/fimmu.2020.536326. https://pubmed.ncbi.nlm.nih.gov/33123124/

4. Tu, Zhenbo, Xiao, Ruijing, Xiong, Jie, Wang, Meng, Zhang, Qiuping. 2016. CCR9 in cancer: oncogenic role and therapeutic targeting. In Journal of hematology & oncology, 9, 10. doi:10.1186/s13045-016-0236-7. https://pubmed.ncbi.nlm.nih.gov/26879872/

5. Koenecke, Christian, Förster, Reinhold. . CCR9 and inflammatory bowel disease. In Expert opinion on therapeutic targets, 13, 297-306. doi:10.1517/14728220902762928. https://pubmed.ncbi.nlm.nih.gov/19236152/

6. Wu, Xue, Wang, Zheng, Liang, Zhenxing, Wei, Jinhong, Yang, Yang. 2024. Pleiotropic role of CCR9/CCL25 signaling in adriamycin-induced cardiomyopathy. In Journal of advanced research, , . doi:10.1016/j.jare.2024.10.018. https://pubmed.ncbi.nlm.nih.gov/39442876/