IL36RN - Interleukin-36 receptor antagonist protein | Elisa - Clia - Antibody - Protein

Background

Interleukin-36 receptor antagonist protein (IL-36Ra), also known as IL-1F5, is part of the interleukin-1 (IL-1) cytokine family, which plays a crucial role in modulating inflammatory and immune responses. IL-36Ra is primarily expressed in epithelial tissues, such as the skin, lungs, and gastrointestinal tract. It functions as an antagonist to the IL-36 cytokines (IL-36α, IL-36β, and IL-36γ), which are potent pro-inflammatory mediators. By binding to the IL-36 receptor (IL-36R) without inducing signal transduction, IL-36Ra inhibits the receptor's activation by IL-36 cytokines, thereby modulating inflammatory responses. This regulatory mechanism is essential in maintaining immune homeostasis and preventing excessive inflammation, which can lead to various inflammatory diseases.

Protein Structure

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

• Pro-IL-36Ra: The inactive precursor form, which is approximately 17-24 kDa in size, depending on post-translational modifications.
• Mature IL-36Ra: The biologically active form, generated through cleavage by specific proteases.

IL-36Ra has a typical β-trefoil fold, a structural motif common among IL-1 family cytokines, which is crucial for its interaction with the IL-36 receptor and its inhibitory function.

Classification and Subtypes

IL-36Ra belongs to the IL-36 subfamily within the broader IL-1 cytokine family. This subfamily includes:

• IL-36α (IL-1F6)
• IL-36β (IL-1F8)
• IL-36γ (IL-1F9)

These cytokines interact with the IL-36 receptor to regulate various inflammatory and immune processes.

Function and Biological Significance

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

• Anti-inflammatory Activity: IL-36Ra competes with IL-36α, IL-36β, and IL-36γ for binding to the IL-36 receptor, thereby preventing their pro-inflammatory signaling.
• Regulation of Immune Responses: By inhibiting IL-36 cytokines, IL-36Ra helps maintain immune homeostasis and prevents excessive inflammatory responses.
• Skin Immunity: IL-36Ra plays a significant role in regulating skin immunity, counteracting the pro-inflammatory effects of IL-36 cytokines in conditions such as psoriasis and atopic dermatitis.

Clinical Issues

Dysregulation or deficiency of IL-36Ra is associated with several inflammatory diseases:

• Psoriasis: Reduced levels or mutations of IL-36Ra are linked to the exacerbation of psoriatic lesions, leading to increased keratinocyte proliferation and inflammation.
• Generalized Pustular Psoriasis (GPP): Mutations in the IL36RN gene, which encodes IL-36Ra, are strongly associated with GPP, a severe and potentially life-threatening form of psoriasis.
• Inflammatory Bowel Disease (IBD): Altered IL-36Ra expression is implicated in the inflammatory processes within the gut in conditions such as Crohn's disease and ulcerative colitis.
• Systemic Inflammation: Deficiency in IL-36Ra can lead to uncontrolled systemic inflammation, contributing to various autoimmune and inflammatory disorders.

Summary

Interleukin-36 receptor antagonist protein (IL-36Ra) is a key anti-inflammatory cytokine in the IL-1 family, primarily expressed in epithelial tissues. It acts by inhibiting the IL-36 receptor, preventing the pro-inflammatory signaling of IL-36α, IL-36β, and IL-36γ. IL-36Ra plays a crucial role in maintaining immune homeostasis and regulating inflammatory responses, particularly in the skin. Dysregulation or mutations in IL-36Ra are associated with several inflammatory diseases, including psoriasis and generalized pustular psoriasis. Understanding the mechanisms and roles of IL-36Ra is essential for developing targeted therapies for these conditions.