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.

Case Study 1: Jens-Alexander Fuchs, 2019

Short linear peptides can overcome certain limitations of small molecules for targeting protein-protein interactions (PPIs). Herein, the interaction between the human chemokine CCL19 with chemokine receptor CCR7 was investigated to obtain receptor-derived CCL19-binding peptides. After identifying a linear binding site of CCR7, five hexapeptides binding to CCL19 in the low micromolar to nanomolar range were designed, guided by pharmacophore and lipophilicity screening of computationally generated peptide libraries.

Fig1. The respective dissociation constants of the interaction between receptor fragments and CCL19.

Case Study 2: Keiko Nakano, 2024

Allergic asthma is driven largely by allergen-specific TH2 cells, which develop in regional lymph nodes on the interaction of naive CD4+ T cells with allergen-bearing dendritic cells that migrate from the lung. This migration event is dependent on CCR7 and its chemokine ligand, CCL21. However, is has been unclear whether the other CCR7 ligand, CCL19, has a role in allergic airway disease. This study sought to define the role of CCL19 in TH2 differentiation and allergic airway disease. Ccl19-deficient mice were studied in an animal model of allergic asthma. Recombinant CCL19 was added to CD4+ T-cell cultures, and gene expression was assessed by RNA-sequencing and quantitative PCR. The results showed that lungs of Ccl19-deficient mice had less allergic airway inflammation, reduced airway hyperresponsiveness, and less IL-4 and IL-13 production compared with lungs of Ccl19-sufficient animals. Recombinant CCL19 increased phosphorylation of STAT5 and induced expression of genes associated with TH2 cell and IL-2 signaling pathways.

Fig2. Flow cytometric analysis of GATA3+ CD4+ T cells is shown.

Fig3. ELISA of IL-2 in the supernatants of naive CD4+ T cells.

CCL19 has several biochemical functions, for example, CCR chemokine receptor binding,CCR10 chemokine receptor binding,CCR7 chemokine receptor binding. Some of the functions are cooperated with other proteins, some of the functions could acted by CCL19 itself. We selected most functions CCL19 had, and list some proteins which have the same functions with CCL19. You can find most of the proteins on our site.

CCL19 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with CCL19 here. Most of them are supplied by our site. Hope this information will be useful for your research of CCL19.