Ccl20, a chemokine, is the only known high-affinity ligand that binds to CCR6, driving the migration of CCR6-expressing cells like B cells, immature dendritic cells, and Th17 cells. It is mainly produced by epithelial cells, and its expression is upregulated under inflammatory conditions. The CCL20-CCR6 axis is involved in autoimmune diseases, cancer progression, and other pathological conditions, making it an important target for research [1,3].

In autoimmune diseases such as inflammatory bowel disease, psoriasis, rheumatoid arthritis, and multiple sclerosis, disrupting the CCR6-CCL20 interaction reduces disease severity, suggesting its key role in these conditions [1]. In colorectal cancer, Fusobacterium nucleatum promotes cancer metastasis through the miR-1322/CCL20 axis and M2 macrophage polarization. Also, CCL20 derived from colorectal cancer cells recruits regulatory T cells to promote chemoresistance via FOXO1/CEBPB/NF-κB signaling [2,5]. In preeclampsia, CCL20 is upregulated and may serve as a predictive and diagnostic biomarker [4]. In oral squamous cell carcinoma, salivary CCL20 expression is increased and can be used to differentiate patients from healthy volunteers [6]. In prostate cancer, circSMARCC1 promotes tumor progression by regulating CCL20 via miR-1322 and the CCL20-CCR6 axis affects macrophage infiltration and polarization [7]. In pancreatic cancer, VDR promotes cancer progression by activating CCL20-mediated M2 polarization of tumor-associated macrophages [8].

In conclusion, Ccl20 plays crucial roles in autoimmune diseases and multiple types of cancers. Studies related to Ccl20 in these disease areas, though not specifically from KO/CKO mouse models in the provided references, highlight its significance in disease development and progression. Understanding Ccl20's functions provides potential therapeutic targets for these diseases.

References:

1. Meitei, Heikrujam Thoihen, Jadhav, Nandadeep, Lal, Girdhari. 2021. CCR6-CCL20 axis as a therapeutic target for autoimmune diseases. In Autoimmunity reviews, 20, 102846. doi:10.1016/j.autrev.2021.102846. https://pubmed.ncbi.nlm.nih.gov/33971346/

2. Xu, Chaochao, Fan, Lina, Lin, Yifeng, Si, Jianmin, Chen, Shujie. . Fusobacterium nucleatum promotes colorectal cancer metastasis through miR-1322/CCL20 axis and M2 polarization. In Gut microbes, 13, 1980347. doi:10.1080/19490976.2021.1980347. https://pubmed.ncbi.nlm.nih.gov/34632963/

3. Chen, Weilong, Qin, Yuanyuan, Liu, Suling. . CCL20 Signaling in the Tumor Microenvironment. In Advances in experimental medicine and biology, 1231, 53-65. doi:10.1007/978-3-030-36667-4_6. https://pubmed.ncbi.nlm.nih.gov/32060846/

4. Wang, Xiufang, Yip, Ka Cheuk, He, Andong, Zhang, Qiao, Li, Ruiman. 2022. Plasma Olink Proteomics Identifies CCL20 as a Novel Predictive and Diagnostic Inflammatory Marker for Preeclampsia. In Journal of proteome research, 21, 2998-3006. doi:10.1021/acs.jproteome.2c00544. https://pubmed.ncbi.nlm.nih.gov/36301636/

5. Wang, Dan, Yang, Li, Yu, Weina, Yuan, Weitang, Zhang, Yi. 2019. Colorectal cancer cell-derived CCL20 recruits regulatory T cells to promote chemoresistance via FOXO1/CEBPB/NF-κB signaling. In Journal for immunotherapy of cancer, 7, 215. doi:10.1186/s40425-019-0701-2. https://pubmed.ncbi.nlm.nih.gov/31395078/

6. Ueda, Sei, Goto, Mitsuo, Hashimoto, Kengo, Nagao, Toru, Nomoto, Shuji. . Salivary CCL20 Level as a Biomarker for Oral Squamous Cell Carcinoma. In Cancer genomics & proteomics, 18, 103-112. doi:10.21873/cgp.20245. https://pubmed.ncbi.nlm.nih.gov/33608307/

7. Xie, Tao, Fu, Du-Jiang, Li, Zhi-Min, Feng, Ning-Han, Zhao, Shan-Chao. 2022. CircSMARCC1 facilitates tumor progression by disrupting the crosstalk between prostate cancer cells and tumor-associated macrophages via miR-1322/CCL20/CCR6 signaling. In Molecular cancer, 21, 173. doi:10.1186/s12943-022-01630-9. https://pubmed.ncbi.nlm.nih.gov/36045408/

8. Li, Hengzhen, Ruan, Yuli, Liu, Chao, Zhang, Yanqiao, Li, Zhiwei. 2024. VDR promotes pancreatic cancer progression in vivo by activating CCL20-mediated M2 polarization of tumor associated macrophage. In Cell communication and signaling : CCS, 22, 224. doi:10.1186/s12964-024-01578-x. https://pubmed.ncbi.nlm.nih.gov/38600588/