Interleukin-17A (IL-17A) is a key signaling molecule in the immune system. It acts as a messenger, facilitating communication between various immune cells. IL-17A plays a role in the body’s protective responses, helping to combat pathogens and manage inflammatory processes.
What is IL-17A?
IL-17A is a cytokine, a small protein that serves as a communication signal between cells. Cytokines are released by one cell and interact with specific receptors on others, triggering responses that coordinate immune system activities.
The primary producers of IL-17A are a specialized subset of T helper lymphocytes known as Th17 cells. Other innate immune cells also contribute to IL-17A production, including gamma delta T cells, natural killer T cells, and some neutrophils.
IL-17A’s Role in Immunity
IL-17A plays a role in the body’s defense mechanisms, particularly against specific types of infections. It contributes to protection against fungal pathogens, such as Candida albicans, and various extracellular bacterial pathogens, including Klebsiella pneumoniae and Staphylococcus aureus.
IL-17A’s protective actions involve recruiting other immune cells to infection sites. It stimulates chemokines, which guide neutrophils—white blood cells that engulf and destroy pathogens—to the affected area.
IL-17A also orchestrates inflammatory responses necessary for effective pathogen clearance. It induces antimicrobial peptides, such as defensins, by epithelial cells, creating a hostile environment for microbes. It also promotes barrier integrity in tissues like the skin and gut, reinforcing physical defenses against microbial invasion.
IL-17A and Disease
Dysregulation of IL-17A, often involving its excessive production, contributes to various autoimmune and inflammatory diseases. When the immune system mistakenly targets the body’s own tissues, IL-17A can amplify destructive processes. Its persistent presence drives chronic inflammation, leading to tissue damage and characteristic symptoms.
In psoriasis, a chronic skin condition, elevated IL-17A levels are found in affected skin lesions. This cytokine promotes rapid keratinocyte proliferation, leading to the thick, scaly plaques typical of the disease. IL-17A also recruits inflammatory cells to the skin, sustaining the inflammatory cycle.
Psoriatic arthritis, an inflammatory arthritis linked to psoriasis, also involves IL-17A. The cytokine contributes to joint inflammation, leading to pain, swelling, and potential erosion. It promotes osteoclast differentiation, cells responsible for bone resorption, which contributes to joint damage.
Ankylosing spondylitis, a chronic inflammatory disease primarily affecting the spine and large joints, also involves IL-17A. The cytokine contributes to inflammation of the sacroiliac joints and spine, leading to stiffness and reduced mobility. It also influences bone formation, potentially contributing to vertebral fusion.
Certain inflammatory bowel diseases, such as Crohn’s disease and ulcerative colitis, also involve excessive IL-17A activity. While its exact role can be complex, IL-17A can contribute to gut inflammation and barrier dysfunction in some subsets. It promotes pro-inflammatory mediators within the intestinal lining, perpetuating chronic inflammation and tissue damage.
Targeting IL-17A in Medicine
Recognizing IL-17A’s role in chronic inflammatory diseases led to specific therapeutic interventions. These treatments neutralize excessive IL-17A activity or its receptor, reducing inflammation and alleviating disease symptoms.
A prominent class of these therapies involves monoclonal antibodies. These engineered proteins bind to and block the activity of IL-17A or its receptor on cell surfaces. This prevents IL-17A from interacting with its receptors, effectively shutting down its pro-inflammatory signals.
Examples include secukinumab and ixekizumab, which target IL-17A, and brodalumab, which targets the IL-17 receptor A. These medications are administered via injections for conditions like moderate to severe plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis.
These therapeutic strategies have shown effectiveness in clinical trials, leading to improvements in symptoms and quality of life. By specifically interfering with the IL-17A pathway, these treatments offer a more precise approach compared to broader immunosuppressants.