B6-hCCR8 Mouse

The CCR8 gene encodes the C-C chemokine receptor type 8, a 41 kDa G-protein coupled receptor with seven transmembrane regions. This protein functions as a receptor for the chemokine CCL1 (also known as I-309) and is involved in cell migration, particularly for various immune cell types, and thymic cell apoptosis. CCR8 expression is notably found in the thymus and is also highly expressed on subsets of CD4+ memory T lymphocytes (including Th2 effector and regulatory T cells or Tregs), natural killer T (NKT) cells, macrophages, monocytes, and monocyte-derived dendritic cells ^[1]. Its expression is particularly relevant in inflammatory settings, where it guides immune cells to sites of inflammation and infection, such as in the lungs in asthma, and in the skin in atopic dermatitis ^[2]. Associated diseases and conditions include allergic disorders (like asthma and atopic dermatitis) due to its role in promoting Th2-biased immune responses, various cancers (e.g., malignant melanoma, hepatocellular carcinoma, cutaneous T-cell lymphomas) where it is highly expressed on tumor-infiltrating Tregs contributing to an immunosuppressive tumor microenvironment, and chronic inflammatory conditions such as chronic obstructive pulmonary disease (COPD) and potentially multiple sclerosis (MS) ^[3]. CCR8 also acts as an alternative co-receptor for HIV-1 infection ^[4].

The B6-hCCR8 mouse is a humanized model, constructed by replacing the coding sequences of the endogenous mouse Ccr8 gene with the coding sequences of the human CCR8 gene. B6-hCCR8 mice can be used for research into the pathogenesis of allergic disorders, various cancers, chronic inflammatory conditions, and HIV-1 infection, as well as for the screening, development, and safety evaluation of CCR8-targeted drugs.