Ccl8, also known as MCP-2, is a chemoattractive cytokine involved in various immune-related pathologies. It is associated with the CCL signaling pathway and plays a role in mediating inflammatory responses, cell recruitment, and cytokine induction [1,2,5]. Genetic models, such as gene knockout (KO) mouse models, have been crucial in studying its functions [4].

In a Ccl8-deficient murine model, the early mortality of acute graft-versus-host disease (aGVHD) was significantly reduced, with a prolonged median survival. This indicates that Ccl8 plays a major role in aGVHD pathogenesis, possibly through an IL-6 signaling cascade [4]. In postpartum breast cancer, Ccl8-deficient animals showed that Ccl8 accelerates tumor onset during mammary gland involution by recruiting M2 subtype macrophages, highlighting its role in this disease [2]. Also, in kidney transplantation, blocking CCL8-CCR8, which is related to the function of Ccl8, significantly inhibits early allograft immune cell infiltration and promotes better short-term allograft function [3].

In conclusion, Ccl8 is a key cytokine in immune-related processes. KO mouse models have revealed its importance in diseases like aGVHD, postpartum breast cancer, and kidney transplantation. Understanding Ccl8's functions provides insights into the mechanisms of these diseases and may offer potential therapeutic targets.

References:

1. Naderi, Asieh, Farmaki, Elena, Chavez, Bernardo, Chatzistamou, Ioulia, Kiaris, Hippokratis. 2022. Beneficial effects of CCL8 inhibition at lipopolysaccharide-induced lung injury. In iScience, 25, 105520. doi:10.1016/j.isci.2022.105520. https://pubmed.ncbi.nlm.nih.gov/36404927/

2. Farmaki, Elena, Kaza, Vimala, Chatzistamou, Ioulia, Kiaris, Hippokratis. 2020. CCL8 Promotes Postpartum Breast Cancer by Recruiting M2 Macrophages. In iScience, 23, 101217. doi:10.1016/j.isci.2020.101217. https://pubmed.ncbi.nlm.nih.gov/32535027/

3. Dangi, Anil, Husain, Irma, Jordan, Collin Z, Kwun, Jean, Luo, Xunrong. 2022. Blocking CCL8-CCR8-Mediated Early Allograft Inflammation Improves Kidney Transplant Function. In Journal of the American Society of Nephrology : JASN, 33, 1876-1890. doi:10.1681/ASN.2022020139. https://pubmed.ncbi.nlm.nih.gov/35973731/

4. Igarashi, Keita, Hori, Tsukasa, Yamamoto, Masaki, Kawasaki, Yukihiko, Kokai, Yasuo. 2021. CCL8 deficiency in the host abrogates early mortality of acute graft-versus-host disease in mice with dysregulated IL-6 expression. In Experimental hematology, 106, 47-57. doi:10.1016/j.exphem.2021.11.006. https://pubmed.ncbi.nlm.nih.gov/34808257/

5. Boss-Kennedy, A, Kim, D, Barai, P, Reyes-Ordoñez, A, Chen, J. . Muscle cell-derived Ccl8 is a negative regulator of skeletal muscle regeneration. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 38, e23841. doi:10.1096/fj.202400184R. https://pubmed.ncbi.nlm.nih.gov/39051762/