Interleukin-23, commonly referred to as IL-23, is a protein that plays a role in the body’s immune system. These proteins, known as cytokines, act as signaling molecules, facilitating communication between cells to coordinate immune responses and manage inflammation. IL-23 helps regulate how the immune system responds to various challenges.
IL-23’s Role in Immunity
IL-23 functions within the immune system primarily by promoting inflammation and activating specific immune cells. It belongs to the IL-12 family of cytokines and is composed of two subunits, p19 and p40. This cytokine is mainly produced by activated dendritic cells and macrophages, which are immune cells found in tissues like the skin and intestines.
A key function of IL-23 involves its interaction with T helper 17 (Th17) cells. While IL-6 and TGF-beta initiate the differentiation of naive T cells into Th17 cells, IL-23 maintains and expands these Th17 cells. IL-23 binds to its specific receptor (a heterodimer of IL-12Rβ1 and IL-23R) on Th17 cells, activating signaling pathways that include JAK2 and TYK2. This interaction stabilizes the Th17 phenotype, leading to the release of pro-inflammatory cytokines such as IL-17, IL-21, IL-22, and GM-CSF. These cytokines help the body respond to extracellular fungi and bacteria and contribute to maintaining barrier tissue integrity.
IL-23’s Link to Disease
Dysregulated IL-23 activity is connected to the development and progression of autoimmune and inflammatory diseases. When the body produces too much IL-23, it can lead to increased inflammation, particularly in the skin, joints, and gut. This overabundance can contribute to chronic autoimmune conditions, including psoriasis, psoriatic arthritis, and inflammatory bowel diseases like Crohn’s disease and ulcerative colitis.
In conditions like psoriasis, IL-23 promotes the expansion and survival of Th17 cells, which then produce pro-inflammatory cytokines such as IL-17 and IL-22. These cytokines act on skin cells, stimulating their growth and creating chronic inflammation that results in the characteristic scaly plaques. Similarly, in inflammatory bowel diseases, pathogens in the gut can activate the IL-23 pathway to fight infection. If the body struggles to turn off IL-23, it leads to a continuously overactive immune system. This triggers cells in the lining of the intestine and colon to multiply inappropriately and produce inflammatory factors, causing tissue damage.
Treatments Targeting IL-23
Therapeutic strategies have been developed to target and modulate IL-23 activity for disease management. These treatments often involve IL-23 inhibitors, a class of biologic drugs designed to block IL-23 from interacting with its receptor. These inhibitors are typically monoclonal antibodies that bind to the p19 subunit of IL-23, preventing inflammatory pathway activation.
By blocking IL-23, these medications disrupt the IL-23/Th17 axis, reducing pro-inflammatory cytokine production and decreasing inflammation. This targeted approach helps alleviate symptoms and promotes tissue healing in conditions like psoriasis, psoriatic arthritis, and Crohn’s disease. The specificity of IL-23 inhibitors helps to minimize broad immune suppression, leading to a favorable safety profile compared to some other immunosuppressive therapies. These treatments have shown efficacy in managing chronic inflammation and improving quality of life for individuals with these autoimmune conditions.