IL36B - Interleukin-36 beta | Elisa - Clia - Antibody - Protein

Background

Interleukin-36 beta (IL-36β), also known as IL-1F8, is part of the interleukin-1 (IL-1) cytokine family, which is pivotal in regulating inflammatory and immune responses. IL-36β is primarily expressed in epithelial tissues, including the skin, lungs, and gastrointestinal tract. Its primary role involves mediating inflammatory responses, particularly in skin-related conditions like psoriasis. IL-36β is released in response to cellular stress or damage and interacts with the IL-36 receptor (IL-36R), composed of IL-1 receptor-like 2 (IL1RL2) and IL-1 receptor accessory protein (IL1RAcP). This interaction triggers signaling pathways, notably NF-κB and MAPK, leading to the production of various pro-inflammatory cytokines and chemokines. IL-36β's functions and regulatory mechanisms make it significant in both innate and adaptive immunity.

Protein Structure

IL-36β is synthesized as a precursor protein that must undergo proteolytic processing to become active:

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

IL-36β has a typical β-trefoil fold structure, which is a common feature among IL-1 family cytokines and is essential for its interaction with the IL-36 receptor and subsequent biological activity.

Classification and Subtypes

IL-36β is a member of the IL-36 subfamily within the IL-1 cytokine family. This subfamily includes:

• IL-36α (IL-1F6)
• IL-36γ (IL-1F9)
• IL-36 receptor antagonist (IL-36Ra or IL-1F5)

These cytokines interact with the IL-36 receptor and play complementary roles in regulating inflammatory processes.

Function and Biological Significance

IL-36β has several important functions:

• Pro-inflammatory Activity: IL-36β stimulates the production of pro-inflammatory cytokines, chemokines, and antimicrobial peptides by keratinocytes, dendritic cells, and macrophages.
• Amplification of Inflammation: It enhances the inflammatory response by acting synergistically with other cytokines such as IL-1β, TNF-α, and IL-17.
• Skin Immunity Regulation: IL-36β plays a crucial role in skin immunity, promoting the activation and recruitment of immune cells to sites of infection or injury. This is particularly relevant in conditions like psoriasis, where it drives local inflammation.
• Modulation of Adaptive Immunity: IL-36β influences adaptive immune responses by promoting the differentiation and function of T cells, especially Th1 and Th17 cells.

Clinical Issues

Dysregulation of IL-36β is linked to various inflammatory diseases:

• Psoriasis: Elevated IL-36β levels are found in psoriatic lesions, contributing to keratinocyte proliferation and inflammation.
• Inflammatory Bowel Disease (IBD): IL-36β is implicated in the inflammatory processes within the gut in conditions like Crohn's disease and ulcerative colitis.
• Rheumatoid Arthritis: IL-36β contributes to the inflammation and joint damage characteristic of rheumatoid arthritis.
• Respiratory Diseases: IL-36β plays a role in respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD), where it contributes to airway inflammation.

Summary

Interleukin-36 beta (IL-36β) is a significant pro-inflammatory cytokine in the IL-1 family, involved in regulating inflammatory responses primarily in epithelial tissues. It acts through the IL-36 receptor, triggering pathways that lead to inflammation and immune cell activation. IL-36β is particularly relevant in skin diseases like psoriasis but also plays roles in inflammatory bowel disease, rheumatoid arthritis, and respiratory conditions. Understanding the mechanisms and effects of IL-36β is crucial for developing targeted therapies for these inflammatory diseases.