The CC chemokine CCL1 is expressed predominantly by endothelial cells, monocytes and other lymphocytes. It is a like cell chemoattractant signaling through CC chemokines receptor-8 (CCR8). CCR8 only recognizes I-309 (mouse TCA-3) and viral chemokines. No other chemokines have been proven to interact with this receptor. Though classified as a CC chemokines, I-309 actually contains 3 disulfide bonds. It is a 96 amino acid protein with a hydrophobic signal sequence that is cleaved upon release.

I-309 (mouse TCA-3) is most often induced by inflammation triggers such as LPS. Stimulation of the T-cell receptor leads to I-309 production. TH2 cells also preferentially express CCR8 promoting an over-recruitment of I-309. In addition, the presence of IL-12 or IFNa will downregulate I-309 production. Also, regulatory T cells selectively express CCR4 and CCR8 and are particularly responsive to I-309, TARC, and MDC chemokines. These events together may help explain the TH1/TH2 decision process by controlling TH1 and TH2 recruitment. Besides inflammation and T-cell regulation, I-309 has been shown to also be involved in angiogenesis. It has also been shown to be a contributor to various diseases. During athersclerosis, monocytes are attracted to the vessel wall of an atherosclerotic plaque. Endothelial cell production of I-309 has been shown to be induced by Lipoprotein(ApoA), a known risk factor for atherosclerosis. I-309 has also been shown to promote cancer survival in T-cell leukemias through anti-apoptotic signal protection.

In summary, CCL1 (I-309) is expressed in numerous inflammatory responses and disease states. It’s involvement in TH1/TH2 regulation makes it particularly important to host immunity. Best assayed in conjunction with factors such as IL-2, IL-4, IL-6, IL-10, IL-12, TNFa, IFNy, MDC, TARC, etc. when understanding T-cell signaling. When studying inflammation and inflammatory diseases, it is best assayed in conjunction with other chemokines (eg. RANTES, MCP-1, MCP-2, MIP-1a), and inflammatory cytokines like IL-1a, IL-1b, IL-6, IFNy, TNFa, and GM-CSF.