Chemokine (C-C motif) ligand 20, commonly known as CCL20, is a signaling protein that guides various cells to specific locations to coordinate responses. This molecule acts as a chemical messenger, influencing a wide array of biological processes.
Understanding CCL20
CCL20 belongs to a family of small proteins called chemokines, which are molecular signals that direct the movement of cells within tissues. It is also known by other names such as macrophage inflammatory protein-3 alpha (MIP-3α) or liver and activation-regulated chemokine (LARC). These proteins act as chemical “beacons” that cells follow.
This chemokine is produced by various cell types and tissues. Epithelial cells, which form the linings of organs like the gut, lungs, and skin, are producers of CCL20. It is also found in the liver and colon, and can be secreted by immune cells such as neutrophils, natural killer (NK) cells, and certain types of T and B cells.
CCL20 exerts its effects by binding to a specific protein on the surface of target cells called CC chemokine receptor 6 (CCR6). CCR6 is unique because it is the only known high-affinity receptor for CCL20. When CCL20 attaches to CCR6, it triggers events inside the cell, prompting movement towards the chemokine source.
How CCL20 Influences the Immune System
CCL20 orchestrates the movement of immune cells, attracting specific types to particular locations. By binding to its receptor CCR6, CCL20 guides immature dendritic cells, certain T cells, and B cells. This directed migration is a fundamental aspect of immune surveillance, enabling cells to detect and respond to threats.
The guidance provided by CCL20 ensures immune cells reach sites needed for defense or normal immune processes. For instance, it contributes to the recruitment of CCR6-expressing B cells to lymphoid structures in the gut, which are important for mucosal immunity. This directed movement helps maintain immune homeostasis.
CCL20 also participates in the early stages of inflammatory responses. When tissues are injured or infected, CCL20 production can increase significantly, helping to initiate the movement of immune cells to these areas. This influx of immune cells is part of the body’s immediate defense mechanism, aiming to clear pathogens or repair damaged tissue. CCL20 can thus function as both a homeostatic and an inflammatory chemokine, depending on the context.
CCL20 and Disease Pathways
Dysregulation of CCL20, meaning either too much or too little is produced, can contribute to various health conditions where the immune system is overactive. Increased CCL20 levels are often observed in inflammatory environments. This can lead to the continued attraction of immune cells and the release of pro-inflammatory signals, potentially prolonging an inflammatory response.
In autoimmune diseases, the immune system mistakenly attacks healthy body tissues. The CCL20-CCR6 axis has been implicated in conditions like inflammatory bowel disease (IBD), psoriasis, rheumatoid arthritis, and multiple sclerosis. In these diseases, CCL20 can contribute to attracting immune cells to healthy tissues, leading to chronic inflammation and tissue damage. Genome-wide association studies have shown a strong correlation between CCR6 expression and the severity of these conditions.
CCL20 also has a complex role in cancer progression. It can directly promote tumor growth and the spread of cancer cells to other parts of the body, known as metastasis. This chemokine can attract immune cells into the tumor microenvironment that, instead of fighting the cancer, may actually suppress anti-tumor responses or support tumor survival. CCL20 is associated with various cancers, including hepatocellular carcinoma, colorectal cancer, breast cancer, pancreatic cancer, cervical cancer, and lung adenocarcinoma.
In the context of infectious diseases, CCL20 plays a dual role. It can contribute to the body’s defense by attracting immune cells to clear pathogens, such as in responses to Yersinia enterocolitica. CCL20 also possesses direct antimicrobial properties, showing activity against certain bacteria and even parasites like Cryptosporidium parvum. However, in some infections, like Cryptosporidium parvum, the body’s production of CCL20 might be reduced, which can hinder the clearance of the pathogen.