Ccl19-KO Mouse

Ccl19, also known as Chemokine (C-C motif) ligand 19, is a homeostatic chemokine abundantly expressed in the thymus and lymph nodes. It primarily regulates immune cell trafficking and is involved in various biological processes such as T cell activation, immune tolerance, and inflammatory responses. It acts through interaction with its cognate receptor CCR7, and the CCL19-CCR7 axis plays a crucial role in the onset of adaptive immunity, with its signaling pathways influencing viral pathogenesis, immune surveillance, and homeostasis [5].

In cancer research, Ccl19 seems to have a dual-edged role. Ccl19-producing fibroblasts promote the formation of tertiary lymphoid structures (TLSs) in colorectal cancer liver metastasis, enhancing the anti-tumor IgG response. CCL19 treatment also promotes TLS neogenesis and prevents tumor growth in mice [1]. In chimeric antigen receptor (CAR)-T cell therapy for solid tumors, engineering CAR-T cells to secrete CCL19 enhances their expansion, migration, and tumor-suppressing abilities. For example, in hepatocellular carcinoma and pancreatic carcinoma xenografts, 7×19 CAR-T cells (secreting IL-7 and CCL19) show superior tumor suppression compared to conventional CAR-T cells [2,3]. In triple-negative breast cancer, CCL19-expressing dendritic cells are associated with favorable responses to anti-PD-(L)1 immunotherapy, and Ccl19 gene ablation dampens CCR7+CD8+ T cells and tumor elimination in response to anti-PD-1 [4].

In allergic airway disease, Ccl19-deficient mice have less allergic airway inflammation, reduced airway hyper-responsiveness, and less IL-4 and IL-13 production, indicating that CCL19 promotes type 2 T-cell differentiation and allergic airway inflammation [6]. In a mouse model of chronic hepatitis B, CCL19 overexpression leads to rapid clearance of intrahepatic HBV through increased intrahepatic CD8+ T-cell proportion and other immune-related mechanisms [7].

In conclusion, Ccl19 is a key regulator in immune-related processes. Model-based research, especially using gene-knockout mouse models in various disease areas such as cancer, allergic airway disease, and viral infection, has revealed its diverse functions. In cancer, it can either promote anti-tumor immune responses or act as a tumor-supportive factor, while in allergic airway disease it contributes to inflammation, and in HBV infection it aids in virus clearance. These findings provide valuable insights into potential therapeutic strategies targeting Ccl19 in different diseases.