Ccl17, also known as thymus-and activation-regulated chemokine (TARC), is a C-C chemokine ligand that binds to C-C chemokine receptor type 4 (CCR4). It plays important roles in immune-related processes, especially in leukocyte recruitment and T-cell-driven diseases. Granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling is a key regulator of Ccl17 expression through cooperative activation of STAT5 and canonical NF-κB signaling [1,2].

Gene knockout studies have provided crucial insights. In Ccl17 knockout mice, reduced left ventricular (LV) remodeling, decreased myocardial fibrosis and cardiomyocyte hypertrophy, and improved LV systolic function were observed after myocardial infarction and angiotensin II and phenylephrine infusion. This was due to increased abundance of regulatory T cells (Tregs) in the myocardium, as Ccl17 inhibits Treg recruitment through biased activation of CCR4 [1]. In addition, Ccll7-KO significantly repressed aging and angiotensin II-induced cardiac hypertrophy and fibrosis, accompanied by the plasticity and differentiation of T cell subsets [3].

In conclusion, Ccl17 is a pro-inflammatory mediator involved in multiple disease processes. Gene knockout mouse models have revealed its role in myocardial injury, cardiac hypertrophy, and heart failure, highlighting its potential as a therapeutic target in these disease areas.

References:

1. Feng, Guoshuai, Bajpai, Geetika, Ma, Pan, Kreisel, Daniel, Lavine, Kory J. 2022. CCL17 Aggravates Myocardial Injury by Suppressing Recruitment of Regulatory T Cells. In Circulation, 145, 765-782. doi:10.1161/CIRCULATIONAHA.121.055888. https://pubmed.ncbi.nlm.nih.gov/35113652/

2. Lupancu, Tanya J, Eivazitork, Mahtab, Hamilton, John A, Achuthan, Adrian A, Lee, Kevin M-C. 2023. CCL17/TARC in autoimmunity and inflammation-not just a T-cell chemokine. In Immunology and cell biology, 101, 600-609. doi:10.1111/imcb.12644. https://pubmed.ncbi.nlm.nih.gov/36975092/

3. Zhang, Yang, Ye, Yicong, Tang, Xiaoqiang, Tian, Zhuang, Zhang, Shuyang. 2022. CCL17 acts as a novel therapeutic target in pathological cardiac hypertrophy and heart failure. In The Journal of experimental medicine, 219, . doi:10.1084/jem.20200418. https://pubmed.ncbi.nlm.nih.gov/35687056/