Ccl8, also known as MCP-2, is a chemoattractive cytokine associated with the CCL signaling pathway. It plays a significant role in various immune-related processes, such as mediating inflammatory responses and regulating cell recruitment [3].

In cancer, Ccl8 has been shown to promote tumor-associated macrophage (TAM) infiltration and reprogramming. In Lewis lung carcinoma-bearing mice, hypofractionated radiotherapy enhances Ccl8-high macrophage infiltration and their roles in macrophage recruitment through the CCL signaling pathway, creating an immunosuppressive tumor microenvironment [1]. In postpartum breast cancer, Ccl8 accelerates tumor onset during mammary gland involution by recruiting M2 subtype macrophages [2].

In kidney transplantation, donor kidney resident macrophages rapidly expand and express high levels of Ccl8, promoting recipient monocyte graft infiltration. Blocking the CCL8-CCR8 axis reduces early allograft immune cell infiltration [4]. In acute graft-versus-host disease (aGVHD), Ccl8 knockout (CCL8-/-) mice exhibit significantly reduced mortality, suggesting Ccl8 plays a major role in aGVHD pathogenesis [5].

In skeletal muscle regeneration, knockdown of Ccl8 in muscle progenitor cells accelerates muscle regeneration, indicating muscle cell-derived Ccl8 negatively regulates this process [6].

In conclusion, Ccl8 is a crucial cytokine involved in immune-related processes and disease development. Studies using Ccl8 knockout mouse models have revealed its role in cancer, transplantation-related diseases, and muscle regeneration, providing valuable insights into disease mechanisms and potential therapeutic targets.