What Is the Chemokine CCL28 and Its Functions?

The immune system uses small signaling proteins called chemokines to direct immune cells where they are needed. One such protein is Chemokine Ligand 28 (CCL28), which belongs to the CC chemokine subgroup and is also known as mucosae-associated epithelial chemokine (MEC). CCL28 guides the movement of specific defensive cells, a process called chemotaxis. By issuing these chemical signals, it helps organize immune responses, particularly at the body’s surfaces.

How CCL28 Directs Immune Cells

The primary function of CCL28 is to act as a chemical attractant for immune cells by binding to receptors on their surface. The two main receptors that recognize CCL28 are Chemokine Receptor 3 (CCR3) and Chemokine Receptor 10 (CCR10). Binding to one of these receptors instructs the cell to move toward the source of the CCL28 signal.

Different immune cells carry different receptors, allowing CCL28 to recruit a specific team of defenders. The CCR10 receptor is found on certain B cells and T cells, and CCL28 effectively attracts plasma cells that produce the antibody Immunoglobulin A (IgA). The CCR3 receptor is expressed on eosinophils, a white blood cell involved in allergic reactions and fighting certain infections. These two pathways allow CCL28 to summon a tailored mix of immune cells.

Protecting the Body’s Surfaces

CCL28 plays a specialized role in mucosal immunity, which defends surfaces exposed to the outside world like the respiratory and gastrointestinal tracts. Epithelial cells, which form the outer layer of these tissues, produce high levels of CCL28. Significant concentrations are found in the salivary glands, mammary glands, colon, and lungs, creating a chemical gradient that draws immune cells to these barrier locations.

This system recruits the IgA-producing plasma cells mentioned earlier. Once in mucosal tissues, these cells secrete large quantities of IgA antibodies into the mucus layer. This antibody acts as a frontline defense, neutralizing pathogens like bacteria and viruses before they can enter the body’s tissues. The constant presence of CCL28 in these areas ensures that IgA-secreting cells are always positioned at these vulnerable entry points to maintain a state of readiness.

The expression of CCL28 creates a common mucosal immune system, where cells activated at one site can be recruited to other distant mucosal surfaces. For example, immune cells that first encounter a pathogen in the airways can be guided by CCL28 to the gut lining. This mechanism allows the body to distribute its defenses broadly across all environmental interfaces.

Direct Action Against Microbes

CCL28 possesses a second, more direct method of fighting infections through broad-spectrum antimicrobial properties. This allows it to attack and kill a range of pathogens on its own, providing another layer of protection at mucosal surfaces. Research shows CCL28 is effective against various gram-positive and gram-negative bacteria, and some fungi like Candida albicans.

This antimicrobial activity is linked to the protein’s C-terminal tail, a section rich in positively charged amino acids not involved in receptor binding. This positively charged domain allows the protein to interact with and disrupt the negatively charged outer membranes of microbes. This interaction compromises the pathogen’s membrane, leading to its death, making CCL28 a dual-function protein.

Connection to Inflammatory Conditions

While CCL28 functions are beneficial, its activity must be tightly regulated. Excessive or ill-timed production can contribute to chronic inflammatory diseases. In these conditions, the normally helpful process of recruiting immune cells becomes dysregulated, leading to persistent inflammation and tissue damage as the same protective mechanisms become drivers of disease.

One example is allergic asthma, where elevated CCL28 levels in the airways recruit large numbers of eosinophils. These cells release substances that cause inflammation and damage to lung tissue, contributing to asthma symptoms.

CCL28 is also implicated in inflammatory bowel diseases (IBD), such as Crohn’s disease and ulcerative colitis. Its expression is increased in the inflamed intestinal tissue of IBD patients. This likely contributes to the excessive accumulation of immune cells in the gut lining, perpetuating the cycle of inflammation. In these contexts, CCL28 acts as an amplifier of the inflammatory response.

A Role in Mother and Infant Health

CCL28’s role in mucosal immunity is apparent in mother and infant health. During lactation, epithelial cells in the mammary glands produce high levels of CCL28, which is secreted into breast milk. This transfers a form of passive immunity to an infant whose own defenses are still maturing.

When an infant consumes breast milk, the CCL28 travels to their gastrointestinal tract. There, it acts as a homing signal, recruiting the mother’s IgA-producing plasma cells, also transferred via the milk, to the infant’s gut lining. These maternal cells then produce IgA antibodies that coat the infant’s intestinal surface, providing protection against ingested pathogens.

This transfer of immunity highlights the protein’s role in conferring protection across generations. By ensuring the infant’s gut is populated with the mother’s antibody-producing cells, CCL28 helps safeguard the newborn’s health while its own immune system gradually develops.