IL1R - Interleukin 1 Receptor Type | Elisa - Clia - Antibody - Protein

Background:

The Interleukin 1 Receptor Type (IL1R) is a transmembrane receptor protein that binds interleukin-1 (IL-1) cytokines, including IL-1α and IL-1β. IL1R is a member of the immunoglobulin superfamily and is expressed on the surface of various cell types, including immune cells, endothelial cells, and epithelial cells.After binding of IL-1 cytokines, IL1R undergoes conformational changes and activates intracellular signaling pathways, including the NF-κB and MAPK pathways. These signaling cascades lead to the production of pro-inflammatory cytokines, chemokines, and other mediators, resulting in the amplification of immune responses and inflammation. IL1R signaling is implicated in various physiological and pathological processes, including host defense against infection, inflammation, tissue repair, and autoimmune diseases. Dysregulated IL1R signaling is associated with chronic inflammatory conditions such as rheumatoid arthritis, inflammatory bowel disease, and systemic inflammatory response syndrome. Therapeutically, targeting IL1R signaling has been explored as a strategy to treat inflammatory diseases. IL-1 receptor antagonists, such as Anakinra and Canakinumab, have been developed to block IL1R activation and have shown efficacy in reducing inflammation and improving clinical outcomes in conditions like rheumatoid arthritis, systemic juvenile idiopathic arthritis, and autoinflammatory syndromes. However, modulation of IL1R signaling requires careful consideration due to its essential role in immune responses and tissue homeostasis.

Protein Structure:

IL-1R exists in several forms, with the primary ones being IL-1R type I (IL-1RI) and IL-1R type II (IL-1RII):

• IL-1RI: This is the main signaling receptor. It consists of three extracellular immunoglobulin-like domains, a single transmembrane domain, and an intracellular Toll/IL-1 receptor (TIR) domain that initiates signal transduction.
• IL-1RII: Often considered a decoy receptor, it has a similar extracellular structure but a truncated intracellular domain that does not signal. IL-1RII primarily acts to sequester IL-1 and prevent it from binding to IL-1RI, thereby regulating IL-1 activity.

Classification and Subtypes:

The IL-1 receptor family includes:

• IL-1R Type I (IL-1RI): The primary receptor for IL-1α and IL-1β signaling.
• IL-1R Type II (IL-1RII): Functions mainly as a decoy receptor.
• IL-1RAcP (IL-1 Receptor Accessory Protein): Required for signal transduction through IL-1RI.
• Other Members: Includes IL-1R-related proteins like IL-1RAPL1 and IL-1RAPL2, which have roles in the nervous system and other tissues.

Function and Biological Significance:

• Signal Transduction: Binding of IL-1α or IL-1β to IL-1RI recruits IL-1RAcP, forming a receptor complex that initiates intracellular signaling cascades. These cascades often involve NF-κB and MAPK pathways, leading to the transcription of pro-inflammatory genes.
• Inflammatory Response: IL-1R signaling is crucial for initiating and sustaining inflammation. It upregulates the expression of various inflammatory mediators, including cytokines, chemokines, and adhesion molecules.
• Regulation of Immune Responses: Beyond inflammation, IL-1R signaling influences immune cell activation, differentiation, and migration.

Interactions:

• IL-1 Ligands: IL-1RI binds IL-1α and IL-1β, while IL-1RII can bind these cytokines but does not transduce signals.
• Accessory Proteins: IL-1RAcP is essential for signal transduction through IL-1RI.
• Regulatory Molecules: IL-1RII and IL-1 receptor antagonist (IL-1Ra) modulate the activity of IL-1 by preventing it from activating IL-1RI.

Clinical Issues:

• Inflammatory Diseases: Dysregulation of IL-1R signaling is implicated in various inflammatory and autoimmune diseases, including rheumatoid arthritis, gout, and systemic juvenile idiopathic arthritis.
• Therapeutic Targets: IL-1R and its ligands are targets for therapeutic intervention. Anakinra, an IL-1 receptor antagonist, is used to treat rheumatoid arthritis and other inflammatory conditions.
• Biomarkers: Soluble forms of IL-1 receptors (sIL-1RI and sIL-1RII) can serve as biomarkers for disease activity and treatment response in inflammatory conditions.

Summary:

The IL-1 receptor (IL-1R) family is essential for mediating the effects of IL-1α and IL-1β, key cytokines in the inflammatory response. The primary receptor, IL-1RI, signals in conjunction with IL-1RAcP to activate intracellular pathways that promote inflammation and immune responses. IL-1RII serves as a decoy receptor, modulating the activity of IL-1. Dysregulation of IL-1R signaling is associated with various inflammatory and autoimmune diseases, making it a significant target for therapeutic intervention. Understanding the roles and regulation of IL-1R is crucial for developing effective treatments for these conditions.