IL1RAP - interleukin 1 receptor accessory protein | Elisa - Clia - Antibody - Protein

Background

Interleukin-1 receptor accessory protein (IL1RAP) is a crucial component in the interleukin-1 (IL-1) signaling pathway, which is essential for the body's immune and inflammatory responses. IL1RAP is a member of the interleukin-1 receptor family, which also includes IL-1 receptor type I (IL1R1) and IL-1 receptor type II (IL1R2). This protein functions as a co-receptor, forming a complex with IL1R1 upon IL-1 binding, which then triggers downstream signaling pathways that lead to the activation of various immune responses. IL1RAP is involved in multiple physiological processes including fever induction, pain sensitization, and the activation of immune cells. Its expression is regulated in response to inflammatory stimuli, highlighting its role in modulating immune responses.

Protein Structure

IL1RAP is a type I transmembrane protein composed of several distinct domains:

• Extracellular Domain: Contains three immunoglobulin-like domains that facilitate binding with IL1R1 and the IL-1 ligand.
• Transmembrane Domain: Anchors the protein in the cell membrane, allowing it to interact with intracellular signaling molecules.
• Intracellular Domain: Essential for initiating signal transduction upon ligand binding. This domain interacts with intracellular adaptor proteins such as MyD88, leading to the activation of downstream signaling pathways, including NF-κB and MAPK.

Classification and Subtypes

IL1RAP is classified as part of the interleukin-1 receptor family and is closely associated with other members involved in IL-1 signaling. There are no widely recognized subtypes of IL1RAP, but it can be functionally classified based on its role in different signaling complexes:

• IL-1 Signaling Complex: Formed with IL1R1 and IL-1 ligand, initiating pro-inflammatory signaling.
• IL-33 Signaling Complex: IL1RAP can also form a complex with IL-33 receptor ST2 and IL-33 ligand, which is involved in type 2 immune responses.

Function and Biological Significance

IL1RAP plays several crucial roles in the immune system:

• Pro-inflammatory Signaling: By forming a complex with IL1R1 and IL-1, IL1RAP is integral in initiating inflammatory responses, leading to the activation of NF-κB and MAPK pathways, which induce the expression of inflammatory cytokines and other mediators.
• Immune Cell Activation: It is involved in the activation and differentiation of various immune cells, including macrophages, dendritic cells, and T cells.
• Modulation of Inflammatory Response: Through its interaction with different receptor complexes, IL1RAP modulates the balance between pro-inflammatory and anti-inflammatory signals.
• Role in Diseases: Given its central role in inflammation, IL1RAP is implicated in various inflammatory diseases, autoimmune disorders, and cancers.

Clinical Issues

Dysregulation of IL1RAP is associated with several clinical conditions:

• Inflammatory Diseases: Overexpression or hyperactivation of IL1RAP is linked to chronic inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, and psoriasis.
• Autoimmune Disorders: Abnormal IL1RAP signaling can contribute to autoimmune conditions by exacerbating immune responses against self-antigens.
• Cancer: IL1RAP is overexpressed in certain cancers, including acute myeloid leukemia (AML), where it promotes tumor growth and survival. It is considered a potential therapeutic target in these cancers.
• Therapeutic Target: IL1RAP is being explored as a therapeutic target for developing anti-inflammatory and anti-cancer treatments. Inhibitors or monoclonal antibodies targeting IL1RAP could modulate its signaling pathways and provide clinical benefits in these diseases.

Summary

IL1RAP (interleukin-1 receptor accessory protein) is a key player in the IL-1 signaling pathway, essential for immune and inflammatory responses. It forms complexes with IL-1 receptors, triggering downstream signaling that activates immune responses. The structure of IL1RAP includes extracellular, transmembrane, and intracellular domains that facilitate its function. Dysregulation of IL1RAP is linked to inflammatory diseases, autoimmune disorders, and cancers. As a result, it is a significant target for therapeutic interventions aimed at modulating immune responses and treating related diseases.