Ccr5, a cell membrane protein from the G protein-coupled receptors (GPCR) family, is a crucial modulator for leukocyte activation and mobilization. It plays a significant role in the chemokine system, which mediates acute inflammation by guiding leukocyte migration to damaged or infected tissues. Ccr5 is also an essential co-receptor for HIV-1 entry, with the R5 strain of the virus commonly using it to infect target cells [4,5,7].

Genetic deficiency of Ccr5 confers protection against HIV infection, and Ccr5-targeted therapies are being explored. In metastatic colorectal cancer, low expression of the CCR5/CCL5 axis was associated with improved survival, especially in patients treated with chemotherapy plus cetuximab, while high expression was related to infiltration by negatively prognostic immune cells and increased immune-suppressive proteins [1]. In cancer, Ccr5 promotes immune responses and tumor cell proliferation, invasion, and migration, and also contributes to an immune-suppressive tumor microenvironment, making it a potential therapeutic target [2]. In paclitaxel-induced peripheral neuropathy, blocking Ccr5 suppresses the development of neuropathic nociception as Ccr5 overexpression in dorsal root ganglion is induced by deoxycholic acid [3]. In pulmonary ischemia-reperfusion injury, Ccr5 drives NK cell-associated airway damage, and its blockade reduces NK cell migration and blunts experimental injury [6].

In summary, Ccr5 is important in multiple biological processes and diseases. Its role in HIV infection, cancer, and various other disease conditions has been revealed through functional studies. The study of Ccr5, especially using genetic models like gene knockout (KO) or conditional knockout (CKO) mouse models, provides valuable insights into disease mechanisms and potential therapeutic strategies for treating diseases such as HIV infection, cancer, and related inflammatory conditions.

References:

1. Schlechter, Benjamin L, Stebbing, Justin. 2024. CCR5 and CCL5 in metastatic colorectal cancer. In Journal for immunotherapy of cancer, 12, . doi:10.1136/jitc-2023-008722. https://pubmed.ncbi.nlm.nih.gov/38719543/

2. Hemmatazad, Hossein, Berger, Martin D. 2021. CCR5 is a potential therapeutic target for cancer. In Expert opinion on therapeutic targets, 25, 311-327. doi:10.1080/14728222.2021.1902505. https://pubmed.ncbi.nlm.nih.gov/33719836/

3. Zhong, Shanshan, Liu, Fangxi, Giniatullin, Rashid, Guo, Qianqian, Zhao, Chuansheng. 2023. Blockade of CCR5 suppresses paclitaxel-induced peripheral neuropathic pain caused by increased deoxycholic acid. In Cell reports, 42, 113386. doi:10.1016/j.celrep.2023.113386. https://pubmed.ncbi.nlm.nih.gov/37948181/

4. Qi, Baowen, Fang, Qiang, Liu, Shiyuan, Huang, Yingchun, Shi, Jianyou. 2020. Advances of CCR5 antagonists: From small molecules to macromolecules. In European journal of medicinal chemistry, 208, 112819. doi:10.1016/j.ejmech.2020.112819. https://pubmed.ncbi.nlm.nih.gov/32947226/

5. Brelot, Anne, Chakrabarti, Lisa A. 2018. CCR5 Revisited: How Mechanisms of HIV Entry Govern AIDS Pathogenesis. In Journal of molecular biology, 430, 2557-2589. doi:10.1016/j.jmb.2018.06.027. https://pubmed.ncbi.nlm.nih.gov/29932942/

6. Santos, Jesse, Wang, Ping, Shemesh, Avishai, Greenland, John R, Calabrese, Daniel R. 2023. CCR5 drives NK cell-associated airway damage in pulmonary ischemia-reperfusion injury. In JCI insight, 8, . doi:10.1172/jci.insight.173716. https://pubmed.ncbi.nlm.nih.gov/37788115/

7. Fantuzzi, Laura, Tagliamonte, Maria, Gauzzi, Maria Cristina, Lopalco, Lucia. 2019. Dual CCR5/CCR2 targeting: opportunities for the cure of complex disorders. In Cellular and molecular life sciences : CMLS, 76, 4869-4886. doi:10.1007/s00018-019-03255-6. https://pubmed.ncbi.nlm.nih.gov/31377844/