IL17A - Interleukin 17A | Elisa - Clia - Antibody - Protein

Background:

The Interleukin 17 family is a group of pro-inflammatory cystine knot cytokines primarily produced by T helper 17 cells in response to stimulation with IL-23. IL17A, was previously known in rodents as CTLA8. In humans, The IL-17 family includes IL17A (sometimes referred to as "IL-17"), IL17B, IL17C, IL17D, IL17E (also known as IL-25), and IL17F. One of the most prominent roles of IL-17 is its participation in initiating and mediating proinflammatory responses. IL-17 is commonly associated with allergic reactions and can induce the production of various other cytokines (such as IL-6, G-CSF, GM-CSF, IL-1β, TGF-β, TNF-α), chemokines (including IL-8, GRO-α, and MCP-1), and prostaglandins (e.g., PGE2) from different cell types, including fibroblasts, endothelial cells, epithelial cells, keratinocytes, and macrophages

Protein Structure:

IL-17A is a homodimeric glycoprotein composed of two identical subunits, each containing 155 amino acids. The structure includes:

• Cysteine-Knot Motif: A characteristic feature of IL-17 family cytokines, contributing to its stability and function.
• Receptor Binding Sites: Regions within the protein that interact with its receptor, IL-17RA/IL-17RC complex.

Classification and Subtypes:

IL-17A belongs to the IL-17 cytokine family, which is classified based on structural similarities and functional properties. Other members of this family include IL-17B, IL-17C, IL-17D, IL-17E (also known as IL-25), and IL-17F. IL-17A often acts synergistically with IL-17F, which has similar but distinct functions.

Function and Biological Significance:

• Inflammatory Response: IL-17A is a potent mediator of inflammation. It stimulates the production of pro-inflammatory cytokines (such as IL-6 and TNF-α), chemokines (such as IL-8), and matrix metalloproteinases, which are involved in tissue remodeling.
• Neutrophil Recruitment: IL-17A plays a critical role in recruiting neutrophils to sites of infection or injury, enhancing the body's ability to combat pathogens.
• Autoimmune Diseases: Dysregulation of IL-17A production is implicated in several autoimmune diseases, including psoriasis, rheumatoid arthritis, and multiple sclerosis. IL-17A contributes to the chronic inflammation observed in these conditions.

Interactions:

• IL-17 Receptors: IL-17A exerts its effects by binding to a heterodimeric receptor complex composed of IL-17RA and IL-17RC. This binding triggers intracellular signaling pathways, leading to the expression of target genes involved in inflammation.
• Other Cytokines: IL-17A often works in concert with other cytokines, such as IL-22 and TNF-α, amplifying the inflammatory response.

Clinical Issues:

• Therapeutic Target: Due to its role in inflammatory and autoimmune diseases, IL-17A is a target for therapeutic intervention. Monoclonal antibodies targeting IL-17A (e.g., secukinumab and ixekizumab) have been developed and are used to treat conditions like psoriasis and ankylosing spondylitis.
• Biomarker: Elevated levels of IL-17A in the blood and tissues can serve as a biomarker for disease activity in various inflammatory and autoimmune conditions.

Summary:

IL-17A (Interleukin 17A) is a key pro-inflammatory cytokine produced primarily by Th17 cells. It plays a crucial role in the immune system's response to infections and is involved in the pathogenesis of several inflammatory and autoimmune diseases. IL-17A functions by binding to its receptor complex, IL-17RA/IL-17RC, and activating downstream signaling pathways that promote inflammation. Given its significant role in disease, IL-17A is an important target for therapeutic intervention in conditions such as psoriasis and rheumatoid arthritis. Understanding IL-17A's biology and its interactions is essential for developing effective treatments for inflammatory diseases.