CCL28, also known as CC chemokine ligand 28, is a member of the CC subfamily of chemokines. This small protein plays a crucial role in immune responses and inflammation, particularly in the context of epithelial and mucosal linings. CCL28 is expressed in various tissues, including the skin, respiratory tract, and gastrointestinal tract, and its expression can be induced by various stimuli, including inflammation and infection. The protein exerts its effects by binding to its cognate receptor, CCR10, which is expressed on various immune cells, including T cells, B cells, and neutrophils. CCL28 has been implicated in several physiological and pathological processes, including immune cell trafficking, inflammation, and antimicrobial defense.

Several studies have highlighted the role of CCL28 in innate and adaptive immunity. CCL28 has been shown to play a critical role in the recruitment and activation of immune cells during infection with mucosal pathogens, such as Salmonella and Acinetobacter. In a study by Walker et al. (2024), CCL28 was found to promote neutrophil accumulation in the gut of mice infected with Salmonella and in the lung of mice infected with Acinetobacter, enhancing the immune response against these pathogens[2]. This chemokine has also been shown to display a broad spectrum of antimicrobial activity against gram-negative and gram-positive bacteria, as well as fungi[1].

Furthermore, CCL28 has been implicated in the regulation of angiogenesis and vascular normalization. In a study by Chen et al. (2024), it was shown that CCL28 could promote tumor vascular normalization after anti-angiogenesis therapy by recruiting and metabolic reprogramming pericytes in the tumor microenvironment[3]. This finding suggests that CCL28 may play a role in the regulation of blood vessel formation and function.

CCL28 has also been shown to play a role in cancer development and progression. In a study by Yan et al. (2024), it was demonstrated that CCL28 downregulation could attenuate pancreatic cancer progression through tumor cell-intrinsic and extrinsic mechanisms[5]. Another study by Mergia Terefe et al. (2022) highlighted the role of CCR10/CCL27-CCL28 axis in tumor development, showing that this axis could play both tumor-suppressive and tumor-promoting roles depending on the types of lymphocytes recruited[4].

In addition, CCL28 has been shown to be involved in wound healing. In a study by Chen et al. (2023), it was shown that neutralization of excessive CCL28 could improve wound healing in diabetic mice by reducing inflammation and enhancing angiogenesis[6]. Another study by Chen et al. (2020) demonstrated that CCL28-induced CCR10/eNOS interaction plays an important role in regulating skin wound angiogenesis[7].

Lastly, CCL28 has been implicated in the pathogenesis of autoimmune diseases. In a study by Yu et al. (2022), it was shown that serum CCL28 levels were significantly lower in patients with Sjögren's syndrome (SS) compared to healthy controls, suggesting that CCL28 may be a useful biomarker for the diagnosis and evaluation of SS[8].

In summary, CCL28 is a multifunctional chemokine that plays a crucial role in innate and adaptive immunity, angiogenesis, cancer development, wound healing, and autoimmune diseases. Further research is needed to fully understand the mechanisms underlying the diverse functions of CCL28 and its potential as a therapeutic target.

References:

1. 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/

2. Walker, Gregory T, Perez-Lopez, Araceli, Silva, Steven, Nizet, Victor, Raffatellu, Manuela. 2024. CCL28 modulates neutrophil responses during infection with mucosal pathogens. In eLife, 13, . doi:10.7554/eLife.78206. https://pubmed.ncbi.nlm.nih.gov/39193987/

3. Chen, Ying, Zhang, Zhiyong, Pan, Fan, Li, Yan, Huang, Guichun. 2024. Pericytes recruited by CCL28 promote vascular normalization after anti-angiogenesis therapy through RA/RXRA/ANGPT1 pathway in lung adenocarcinoma. In Journal of experimental & clinical cancer research : CR, 43, 210. doi:10.1186/s13046-024-03135-3. https://pubmed.ncbi.nlm.nih.gov/39075504/

4. Mergia Terefe, Ermias, Catalan Opulencia, Maria Jade, Rakhshani, Amir, Kadhim, Mustafa M, Taherian, Gholamali. 2022. Roles of CCR10/CCL27-CCL28 axis in tumour development: mechanisms, diagnostic and therapeutic approaches, and perspectives. In Expert reviews in molecular medicine, 24, e37. doi:10.1017/erm.2022.28. https://pubmed.ncbi.nlm.nih.gov/36155126/

5. 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/

6. Chen, Zhenlong, Haus, Jacob M, DiPietro, Luisa A, Koh, Timothy J, Minshall, Richard D. 2023. Neutralization of excessive CCL28 improves wound healing in diabetic mice. In Frontiers in pharmacology, 14, 1087924. doi:10.3389/fphar.2023.1087924. https://pubmed.ncbi.nlm.nih.gov/36713846/

7. Chen, Zhenlong, Haus, Jacob M, Chen, Lin, Koh, Timothy J, Minshall, Richard D. 2020. CCL28-induced CCR10/eNOS interaction in angiogenesis and skin wound healing. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 34, 5838-5850. doi:10.1096/fj.201902060R. https://pubmed.ncbi.nlm.nih.gov/32124475/

8. Yu, X, Zhu, F, Yu, X, Wu, B, Li, C. 2022. Serum CCL28 as a biomarker for diagnosis and evaluation of Sjögren's syndrome. In Scandinavian journal of rheumatology, 52, 200-207. doi:10.1080/03009742.2021.2001930. https://pubmed.ncbi.nlm.nih.gov/35048789/