Ccr2, the CC chemokine receptor 2, is a key receptor in the chemokine signaling pathways. It binds to ligands like CCL2, and their interaction plays a pivotal role in numerous biological processes such as cell migration, immune cell recruitment, and inflammation regulation. This CCL2-Ccr2 axis is involved in multiple physiological and pathological conditions [1-10].

In various disease models, the significance of Ccr2 has been revealed. In a chronic headache model induced by repeated nitroglycerin administration, Ccr2 global knockout mice did not exhibit acute or persistent facial skin hypersensitivity as wild-type mice did, indicating that CCL2-Ccr2 signalling in T cells and macrophages is required for chronic headache-related sensitization [1]. In hepatocellular carcinoma models, blocking the CCL2/Ccr2 axis by either using a Ccr2 antagonist or knocking out host Ccr2 inhibited malignant growth, metastasis, and postsurgical recurrence, while enhancing survival. This was due to the inhibition of inflammatory monocyte recruitment, TAM infiltration and M2-polarization, and the subsequent activation of an antitumorous CD8+ T cell response [2]. In osteoarthritis models, mice lacking Ccr2 were protected against OA, with a reduction in local monocyte/macrophage numbers in their joints. Blockade of CCL2/Ccr2 signalling also attenuated macrophage accumulation, synovitis, and cartilage damage [3].

In conclusion, Ccr2, through its interaction with CCL2, is essential in regulating inflammation, immune cell recruitment, and cell migration. Gene knockout mouse models, especially Ccr2 KO models, have significantly contributed to understanding its role in diseases such as chronic headache, hepatocellular carcinoma, and osteoarthritis. These findings highlight Ccr2 as a potential therapeutic target for treating these diseases.

References:

1. Ryu, Sun, Liu, Xuemei, Guo, Tingting, Zhang, Jintao, Cao, Yu-Qing. . Peripheral CCL2-CCR2 signalling contributes to chronic headache-related sensitization. In Brain : a journal of neurology, 146, 4274-4291. doi:10.1093/brain/awad191. https://pubmed.ncbi.nlm.nih.gov/37284790/

2. Li, Xiaoguang, Yao, Wenbo, Yuan, Ya, Jiang, Xiaoqing, Wang, Hui. 2015. Targeting of tumour-infiltrating macrophages via CCL2/CCR2 signalling as a therapeutic strategy against hepatocellular carcinoma. In Gut, 66, 157-167. doi:10.1136/gutjnl-2015-310514. https://pubmed.ncbi.nlm.nih.gov/26452628/

3. Raghu, Harini, Lepus, Christin M, Wang, Qian, Sokolove, Jeremy B, Robinson, William H. 2016. CCL2/CCR2, but not CCL5/CCR5, mediates monocyte recruitment, inflammation and cartilage destruction in osteoarthritis. In Annals of the rheumatic diseases, 76, 914-922. doi:10.1136/annrheumdis-2016-210426. https://pubmed.ncbi.nlm.nih.gov/27965260/