CCL19

Fig1. Schematic of CCR7 and its ligands. (Yan Yan, 2019)

What is CCL19 protein?

CCL19 gene (C-C motif chemokine ligand 19) is a protein coding gene which situated on the short arm of chromosome 9 at locus 9p13. Cytokines are a family of secreted proteins involved in immunoregulatory and inflammatory processes. The CC cytokines are proteins characterized by two adjacent cysteines. The cytokine encoded by this gene may play a role in normal lymphocyte recirculation and homing. It also plays an important role in trafficking of T cells in thymus, and in T cell and B cell migration to secondary lymphoid organs. It specifically binds to chemokine receptor CCR7. The CCL19 protein is consisted of 98 amino acids and CCL19 molecular weight is approximately 11.0 kDa.

What is the function of CCL19 protein?

It is particularly important for the induction of T cell activation, immune tolerance, and inflammatory responses during continuous immune surveillance, homeostasis, and development. The primary function of CCL19 includes attracting dendritic cells and T cells to sites of infection or inflammation, thereby facilitating an immune response. It is also involved in the homing of lymphocytes to secondary lymphoid organs, which is essential for the adaptive immune response. Furthermore, CCL19 has been implicated in the mediation of antitumor effects by promoting the infiltration of immune cells into tumors and potentially inhibiting tumor proliferation, invasion, and migration. In the context of vaccine development, CCL19 contributes to vaccine-based protection against various viruses by stimulating the release of antiviral-associated cytokines, which promote T cell proliferation and antigen uptake by dendritic cells.

CCL19 Related Signaling Pathway

CCL19 plays a critical role in the induction of T cell activation and the migration of T cells to secondary lymphoid organs, which is essential for the adaptive immune response. CCL19 has been reported to have antitumor effects by attracting dendritic cells and T cells to the tumor site, mediating the release of cytokines, and inhibiting tumor proliferation, invasion, and migration. CCL19-induced signaling involves various pathways such as PI3K, NF-κB, and MEK/Ras/Raf, which are suppressed by specific inhibitors and play a role in the context of HIV-1 infection. CCL19, along with CCL21 another CCR7 ligand, has been shown to induce differential signaling networks in multiple cell types, highlighting the complexity of CCR7 signaling.

CCL19 Related Diseases

In cancer, CCL19 has a dual role; it can both promote and inhibit tumor growth depending on the context, with research suggesting it may modulate the tumor immune microenvironment and predict prognosis in breast cancer. In autoimmune diseases, elevated levels of CCL19 have been observed in systemic lupus erythematosus (SLE), where it may be involved in the pathogenesis by affecting B cell subset distribution. Additionally, CCL19 is associated with rheumatoid arthritis (RA), where its serum levels reflect the immune activity state and could potentially guide clinical treatment strategies. Furthermore, CCL19 has been linked to coronary artery disease, where it may be related to metabolic and transport processes of inorganic cations/anions and amino acids/oligopeptides.

Bioapplications of CCL19

It is increasingly recognized for its role in mediating the infiltration of dendritic cells, CD4+, and CD8+ T cells into tumors. The profound impact of CCL19 on the tumor immune microenvironment has placed it under the spotlight for developing novel therapeutic strategies, including its potential to enhance the efficacy of anti-PD-(L)1 immunotherapies in triple-negative breast cancer. Moreover, CCL19's expression is being explored in the context of rheumatic and autoimmune diseases, suggesting a broader scope for its bioapplication. Based on these CCL19 functions, there is a trend to develop CCL19 antibody products or CCL19 ELISA reagents.