Ccl28, also known as mucosae-associated epithelial chemokine (MEC), is a β-or CC chemokine. It plays a crucial role in host immunity at various epithelial and mucosal linings, guiding the chemotactic activity of immune cells in conjunction with its receptors CCR10 and CCR3. Ccl28 is involved in processes such as lymphocyte trafficking, immunomodulation, and has antimicrobial activity, bridging innate and adaptive immunity [2].

In an I/R-induced renal injury mouse model, Alkbh5-knockout mice showed milder renal injury. Ccl28 was identified as a target of ALKBH5, and Ccl28 mRNA stability increased with Alkbh5 deficiency, mediating Treg recruitment and inhibiting inflammatory cells [1]. In pancreatic cancer, CCL28 knockdown in mouse pancreatic cancer cell line PAN02 impaired cell proliferation, and in mouse models, CCL28 deficiency attenuated tumor growth by remodeling the tumor microenvironment [3]. In oral squamous cell carcinoma, CCL28 inhibited bone invasion and EMT in mouse models, and was associated with better patient survival [4].

In conclusion, Ccl28 is essential for immune-related functions at mucosal sites. Gene-knockout mouse models have revealed its role in diseases like renal injury, pancreatic cancer, and oral squamous cell carcinoma, suggesting it could be a potential therapeutic target in these disease areas.

References:

1. Chen, Juntao, Xu, Cuidi, Yang, Kun, Wang, Jina, Zhu, Tongyu. 2023. Inhibition of ALKBH5 attenuates I/R-induced renal injury in male mice by promoting Ccl28 m6A modification and increasing Treg recruitment. In Nature communications, 14, 1161. doi:10.1038/s41467-023-36747-y. https://pubmed.ncbi.nlm.nih.gov/36859428/

2. Mohan, Teena, Deng, Lei, Wang, Bao-Zhong. 2017. CCL28 chemokine: An anchoring point bridging innate and adaptive immunity. In International immunopharmacology, 51, 165-170. doi:10.1016/j.intimp.2017.08.012. https://pubmed.ncbi.nlm.nih.gov/28843907/

3. Yan, Jingjing, Yuan, Pengkun, Gui, Liming, Gao, Wei-Qiang, Ma, Bin. . CCL28 Downregulation Attenuates Pancreatic Cancer Progression Through Tumor Cell-Intrinsic and -Extrinsic Mechanisms. In Technology in cancer research & treatment, 20, 15330338211068958. doi:10.1177/15330338211068958. https://pubmed.ncbi.nlm.nih.gov/34939465/

4. Park, Junhee, Zhang, Xianglan, Lee, Sun Kyoung, Park, Kwang-Kyun, Chung, Won-Yoon. . CCL28-induced RARβ expression inhibits oral squamous cell carcinoma bone invasion. In The Journal of clinical investigation, 129, 5381-5399. doi:10.1172/JCI125336. https://pubmed.ncbi.nlm.nih.gov/31487270/