Interleukins are signaling proteins, also known as cytokines, primarily produced by white blood cells and other body cells. They mediate communication between cells, particularly within the immune system, regulating cellular activities like growth, differentiation, and movement. Interleukin-20 (IL-20) is a specific member of this family, influencing various biological processes.
Understanding Interleukin-20
IL-20 is produced by cell types like keratinocytes in the skin, monocytes, and endothelial cells. Its expression increases during inflammatory responses and tissue repair. IL-20 functions by binding to specific receptors on target cells, initiating a cascade of signals.
There are two main types of IL-20 receptors: Type I, composed of IL-20 receptor alpha and beta subunits, and Type II, formed by the IL-22 receptor and IL-20 receptor beta subunit. Both receptor types bind IL-20 and IL-24, while Type I also binds IL-19. Upon binding, IL-20 activates signaling pathways, such as the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway, with STAT3 being a primary transcription factor activated by both receptor types. This activation influences gene expression, affecting tissue repair, epithelial cell proliferation, and keratinocyte differentiation during inflammation.
Interleukin-20’s Role in Disease
Dysregulated levels or activity of IL-20 are implicated in several human diseases, where it often contributes to inflammation and tissue damage. In psoriasis, a chronic inflammatory skin condition, IL-20 and its receptors are found at elevated levels in affected skin. IL-20 promotes the thickening of the epidermis and stimulates keratinocyte proliferation through immune cells present in the skin.
IL-20 also plays a role in rheumatoid arthritis (RA), an autoimmune disease affecting joints. High levels of IL-20 are found in the synovial fluid of RA patients, and it stimulates synovial fibroblasts to secrete pro-inflammatory molecules like monocyte chemoattractant protein 1 (MCP-1) and IL-8, which attract immune cells to the joints, contributing to inflammation and pain. IL-20 is an upstream regulator of other inflammatory cytokines such as TNF-α, IL-1, and IL-6, all involved in RA progression.
In cancer, IL-20’s role can be complex and is still being explored. It is highly expressed in breast cancer tissues and enhances breast tumor growth by promoting cell proliferation and anti-apoptotic signals. IL-20 has also been linked to increased cancer cell mobility and invasion in breast and bladder cancers.
In non-small cell lung cancer (NSCLC), IL-20 and its receptors are often dysregulated, with elevated levels of IL-20RB protein observed in tumors. Conversely, IL-20 may have anti-angiogenic effects in NSCLC by reducing the expression of vascular endothelial growth factor (VEGF). IL-20 has also been detected in atherosclerotic plaques, suggesting its involvement in the inflammation and vascular remodeling associated with this condition.
Therapeutic Approaches Targeting Interleukin-20
Understanding IL-20’s involvement in various diseases has led to investigations into therapeutic strategies to modulate its activity. A key approach involves blocking IL-20 or its receptors to reduce its pro-inflammatory effects. Monoclonal antibodies are a therapeutic approach being explored for this purpose. These antibodies specifically bind to IL-20 or its receptors, preventing IL-20 from initiating its signaling cascade.
For instance, a selective anti-IL-20 recombinant human monoclonal antibody, NNC0109-0012, has been tested in phase IIa clinical trials for patients with active rheumatoid arthritis. Results indicated that treatment with this antibody led to improvements in disease activity, particularly in seropositive patients, with symptom reductions as early as one week into treatment. This suggests that targeting IL-20 could offer a new avenue for treating conditions driven by chronic inflammation. Research continues to explore the therapeutic potential of IL-20 inhibitors across a range of inflammatory and autoimmune conditions.