IL37 - Interleukin 37 | Elisa - Clia - Antibody - Protein

Background

Interleukin-37 (IL-37), also known as IL-1 family member 7 (IL-1F7), is a member of the interleukin-1 (IL-1) cytokine family. IL-37 is recognized for its anti-inflammatory properties and its ability to suppress immune responses. It is encoded by the IL37 gene, located on chromosome 2. IL-37 is produced as a precursor that requires proteolytic processing to become active. It is expressed in various tissues, including immune cells (macrophages, dendritic cells), epithelial cells, and tissues such as the skin, lungs, and the gastrointestinal tract. IL-37 is induced by inflammatory stimuli and acts as a natural suppressor of immune and inflammatory responses, contrasting with other IL-1 family members that generally promote inflammation.

Protein Structure

IL-37 is synthesized as a precursor protein and undergoes proteolytic cleavage to become fully active. It has several isoforms (A-E) due to alternative splicing:

• Precursor IL-37: The inactive form, requiring cleavage for activation.
• Mature IL-37: The biologically active form, resulting from cleavage by caspase-1.

IL-37 contains the typical β-trefoil structure, which is common among IL-1 family cytokines and is critical for its biological functions. This structure facilitates its binding to receptors and interactions with other signaling molecules.

Classification and Subtypes

IL-37 belongs to the IL-1 family of cytokines, which includes:

• IL-1α
• IL-1β
• IL-18
• IL-33
• IL-36 subfamily (IL-36α, IL-36β, IL-36γ, and IL-36Ra)

IL-37 itself has five known isoforms (IL-37a to IL-37e), generated through alternative splicing, each potentially having distinct functions and tissue distribution.

Function and Biological Significance

IL-37 plays several crucial roles in the immune system:

• Anti-inflammatory Activity: IL-37 suppresses the production of pro-inflammatory cytokines, chemokines, and other inflammatory mediators, thus dampening inflammatory responses.
• Immune Regulation: It reduces the activation of immune cells, such as macrophages and dendritic cells, thereby modulating the immune response.
• Interaction with IL-18Rα and SIGIRR: IL-37 exerts its effects by binding to IL-18 receptor alpha (IL-18Rα) and single immunoglobulin IL-1-related receptor (SIGIRR), leading to the suppression of inflammatory signaling pathways.
• Negative Regulation of Inflammation: It acts as a counter-regulatory mechanism to prevent excessive inflammation, which can lead to tissue damage and autoimmune diseases.

Clinical Issues

Dysregulation of IL-37 is associated with various inflammatory and autoimmune diseases:

• Rheumatoid Arthritis: Reduced levels of IL-37 are observed in patients with rheumatoid arthritis, contributing to increased inflammation and disease severity.
• Inflammatory Bowel Disease (IBD): Altered expression of IL-37 is linked to the pathogenesis of IBD, including Crohn's disease and ulcerative colitis.
• Systemic Lupus Erythematosus (SLE): Lower IL-37 levels are associated with heightened disease activity in SLE patients.
• Metabolic Disorders: IL-37 has been implicated in the regulation of metabolic processes, with dysregulation contributing to conditions like obesity and type 2 diabetes.

Summary

Interleukin-37 (IL-37) is a unique member of the IL-1 cytokine family known for its potent anti-inflammatory properties. It is produced in response to inflammatory stimuli and acts to suppress immune and inflammatory responses, contrasting with the pro-inflammatory roles of other IL-1 family cytokines. IL-37 achieves its effects through interactions with IL-18Rα and SIGIRR, leading to the inhibition of inflammatory signaling pathways. Dysregulation of IL-37 is associated with several inflammatory and autoimmune diseases, making it a potential therapeutic target for conditions characterized by excessive inflammation. Understanding the regulatory mechanisms of IL-37 provides valuable insights into managing these diseases.