IL36A - Interleukin 36 Alpha | Elisa - Clia - Antibody - Protein

Background

Interleukin 36 alpha (IL-36α), also known as IL-1F6, is a member of the interleukin-1 (IL-1) family of cytokines. This family includes several important mediators of the inflammatory response, such as IL-1α, IL-1β, and IL-18. IL-36α is primarily expressed in epithelial tissues, including the skin, lungs, and gastrointestinal tract, where it plays a significant role in local immune responses. It is particularly involved in the pathogenesis of inflammatory skin diseases, such as psoriasis. IL-36α exerts its effects by binding to the IL-36 receptor (IL-36R), which is composed of IL-1 receptor-related protein 2 (IL1RL2) and IL-1 receptor accessory protein (IL1RAcP), triggering downstream signaling pathways that lead to the activation of NF-κB and mitogen-activated protein kinases (MAPKs).

Protein Structure

IL-36α is synthesized as a precursor protein that requires processing to become fully active:

• Pro-IL-36α: The inactive precursor form of IL-36α, which is 17-23 kDa in size, depending on post-translational modifications.
• Mature IL-36α: The biologically active form of IL-36α, generated through cleavage by proteases such as neutrophil-derived cathepsin G or elastase.

IL-36α shares structural similarities with other IL-1 family members, featuring a β-trefoil fold typical of this cytokine family.

Classification and Subtypes

IL-36α is part of the IL-36 subfamily within the IL-1 cytokine family, which also includes IL-36β (IL-1F8), IL-36γ (IL-1F9), and the IL-36 receptor antagonist (IL-36Ra or IL-1F5). These cytokines interact with the IL-36 receptor to modulate inflammatory responses.

Function and Biological Significance

IL-36α plays several critical roles in the immune system:

• Pro-inflammatory Activity: IL-36α promotes the production of pro-inflammatory cytokines, chemokines, and antimicrobial peptides by keratinocytes, dendritic cells, and other immune cells.
• Epidermal Function: IL-36α is involved in skin homeostasis and repair, contributing to the maintenance of the skin barrier and the immune response to pathogens.
• Immune Cell Recruitment and Activation: IL-36α facilitates the recruitment and activation of various immune cells, including T cells, macrophages, and neutrophils, enhancing the local inflammatory response.
• Amplification of Inflammation: IL-36α works synergistically with other cytokines, such as IL-1β and IL-17, to amplify inflammatory signals and responses.

Clinical Issues

Dysregulation of IL-36α is associated with several inflammatory diseases:

• Psoriasis: Elevated levels of IL-36α are found in psoriatic lesions, and it plays a key role in the pathogenesis of this chronic inflammatory skin disease by promoting keratinocyte proliferation and inflammation.
• Inflammatory Bowel Disease (IBD): IL-36α is implicated in the pathogenesis of IBD, contributing to the inflammatory processes in the gut.
• Rheumatoid Arthritis: IL-36α may contribute to the inflammation and joint damage observed in rheumatoid arthritis through its effects on synovial cells and immune cell recruitment.
• Respiratory Diseases: IL-36α is involved in the inflammatory responses in respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD).

Summary

Interleukin 36 alpha (IL-36α) is a pro-inflammatory cytokine in the IL-1 family, primarily expressed in epithelial tissues and playing a crucial role in local immune responses. It acts through the IL-36 receptor, triggering downstream signaling pathways that lead to the activation of inflammatory responses. Dysregulation of IL-36α is implicated in various inflammatory diseases, including psoriasis, IBD, rheumatoid arthritis, and respiratory diseases. Understanding the mechanisms and roles of IL-36α in these conditions provides valuable insights into potential therapeutic targets for managing inflammatory and immune-related disorders.