IL1RL2 - Interleukin 1 Receptor Like Protein 2 | Elisa - Clia - Antibody - Protein

Background

Interleukin 1 Receptor-Like Protein 2 (IL1RL2), also known as IL-1 receptor-related protein 2 or IL-36 receptor, is a member of the interleukin-1 receptor (IL-1R) family. IL1RL2 is part of the signaling complex for IL-36 cytokines, including IL-36α, IL-36β, and IL-36γ. These cytokines are involved in the regulation of immune responses, particularly in the skin and mucosal tissues. IL1RL2, in combination with its co-receptor IL-1 receptor accessory protein (IL1RAcP), mediates the biological effects of IL-36 cytokines, leading to the activation of inflammatory pathways. The receptor is predominantly expressed in epithelial cells and various immune cells, such as dendritic cells and macrophages, playing a critical role in both innate and adaptive immunity.

Protein Structure

IL1RL2 is a type I transmembrane protein composed of several key structural domains:

• Extracellular Domain: This domain includes three immunoglobulin (Ig)-like domains responsible for cytokine binding and receptor dimerization.
• Transmembrane Domain: A single-pass transmembrane helix that anchors the protein to the cell membrane.
• Intracellular Domain: The cytoplasmic tail contains motifs essential for signaling transduction, including recruitment and activation of adaptor proteins such as MyD88, leading to downstream activation of NF-κB and MAPK pathways.

Classification and Subtypes

IL1RL2 belongs to the IL-1 receptor family, which includes several related receptors involved in inflammatory signaling:

• IL1R1: Binds IL-1α and IL-1β.
• IL1RL1 (ST2): Binds IL-33.
• IL1RL2 (IL-36R): Binds IL-36 cytokines.

There are no distinct subtypes of IL1RL2, but its functional diversity is achieved through interactions with different ligands and signaling partners.

Function and Biological Significance

IL1RL2 plays a pivotal role in mediating immune responses, especially in epithelial and mucosal tissues:

• Inflammatory Signaling: IL1RL2, upon binding IL-36 cytokines, activates NF-κB and MAPK signaling pathways, leading to the production of pro-inflammatory cytokines and chemokines.
• Skin Inflammation: IL1RL2 is involved in skin homeostasis and inflammatory skin diseases such as psoriasis, where IL-36 signaling is significantly upregulated.
• Host Defense: Contributes to the defense against pathogens by promoting inflammatory responses and enhancing the activity of immune cells such as macrophages and dendritic cells.
• Tissue Repair: Participates in tissue repair processes by modulating the inflammatory response and promoting the healing of epithelial barriers.

Clinical Issues

Dysregulation of IL1RL2 signaling is associated with several clinical conditions:

• Psoriasis and Other Skin Diseases: Overactivation of IL1RL2 signaling is implicated in psoriasis, leading to excessive inflammation and keratinocyte proliferation.
• Autoimmune Diseases: Aberrant IL1RL2 signaling contributes to the pathogenesis of autoimmune conditions by promoting chronic inflammation.
• Inflammatory Bowel Disease (IBD): Elevated IL1RL2 expression is observed in IBD, suggesting a role in intestinal inflammation.
• Cancer: IL1RL2 signaling may influence the tumor microenvironment, affecting tumor growth and immune evasion mechanisms.

Summary

IL1RL2 (Interleukin 1 Receptor-Like Protein 2) is an essential receptor in the IL-1 receptor family, primarily mediating the effects of IL-36 cytokines. It is involved in activating inflammatory pathways, particularly in epithelial and immune cells. Structurally, IL1RL2 consists of extracellular Ig-like domains, a transmembrane region, and an intracellular signaling domain. The receptor is crucial for skin inflammation, host defense, and tissue repair. Dysregulation of IL1RL2 signaling is linked to various inflammatory and autoimmune diseases, as well as cancer, making it a potential therapeutic target for modulating immune responses. Understanding IL1RL2's role in these processes provides insights into its significance in health and disease.