IL36G - Interleukin-36 gamma | Elisa - Clia - Antibody - Protein

Background

Interleukin-36 gamma (IL-36γ), also known as IL-1F9, is a member of the interleukin-1 (IL-1) cytokine family, which plays a crucial role in the regulation of inflammatory and immune responses. IL-36γ is predominantly expressed in epithelial tissues, such as the skin, lungs, and gastrointestinal tract, and is particularly involved in the host defense against microbial infections and in inflammatory diseases. This cytokine is known for its ability to activate keratinocytes, dendritic cells, and other immune cells, contributing to the amplification of local inflammatory responses. IL-36γ signals through the IL-36 receptor (IL-36R), which consists of IL-1 receptor-like 2 (IL1RL2) and IL-1 receptor accessory protein (IL1RAcP). Upon binding to its receptor, IL-36γ triggers intracellular signaling cascades that lead to the activation of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs), resulting in the production of pro-inflammatory cytokines and chemokines.

Protein Structure

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

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

IL-36γ has a characteristic β-trefoil fold, which is a common structural motif among IL-1 family cytokines, essential for its receptor binding and biological function.

Classification and Subtypes

IL-36γ is part of the IL-36 subfamily within the IL-1 cytokine family. This subfamily includes:

• IL-36α (IL-1F6)
• IL-36β (IL-1F8)
• IL-36 receptor antagonist (IL-36Ra or IL-1F5)

These cytokines interact with the IL-36 receptor to modulate various aspects of inflammatory and immune responses.

Function and Biological Significance

IL-36γ serves several critical functions in the immune system:

• Pro-inflammatory Activity: IL-36γ promotes the production of pro-inflammatory cytokines, chemokines, and antimicrobial peptides by keratinocytes, dendritic cells, and macrophages.
• Amplification of Inflammatory Responses: It acts synergistically with other cytokines, such as IL-1β, TNF-α, and IL-17, to enhance local and systemic inflammatory responses.
• Host Defense: IL-36γ is involved in the defense against microbial infections by promoting the activation and recruitment of immune cells to infection sites.
• Skin Immunity Regulation: IL-36γ is crucial in the regulation of skin immunity, contributing to the pathogenesis of skin inflammatory diseases such as psoriasis and atopic dermatitis.

Clinical Issues

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

• Psoriasis: Elevated levels of IL-36γ are found in psoriatic lesions, contributing to keratinocyte proliferation and inflammation.
• Inflammatory Bowel Disease (IBD): IL-36γ is implicated in the inflammatory processes within the gut in conditions such as Crohn's disease and ulcerative colitis.
• Asthma and Chronic Obstructive Pulmonary Disease (COPD): IL-36γ contributes to airway inflammation and remodeling in respiratory diseases.
• Rheumatoid Arthritis: IL-36γ may play a role in the inflammation and joint damage observed in rheumatoid arthritis.

Summary

Interleukin-36 gamma (IL-36γ) is a potent pro-inflammatory cytokine in the IL-1 family, primarily expressed in epithelial tissues and involved in the regulation of inflammatory and immune responses. It acts through the IL-36 receptor, triggering pathways that lead to inflammation and immune cell activation. IL-36γ is particularly relevant in the pathogenesis of skin diseases like psoriasis, as well as inflammatory bowel disease, respiratory conditions, and rheumatoid arthritis. Understanding the mechanisms and roles of IL-36γ provides valuable insights into potential therapeutic targets for managing these inflammatory diseases.