SIGIRR - Single Ig IL1 Related Receptor | Elisa - Clia - Antibody - Protein

Background

Single Immunoglobulin Interleukin-1 Related Receptor (SIGIRR), also known as Toll/IL-1 receptor 8 (TIR8), is a member of the interleukin-1 receptor (IL-1R) superfamily. SIGIRR is unique within this family due to its function as a negative regulator of Toll-like receptor (TLR) and IL-1R signaling pathways. This receptor plays a crucial role in controlling inflammation and maintaining immune homeostasis. SIGIRR is expressed in various tissues, including immune cells, epithelial cells, and fibroblasts. Its regulatory functions are essential for preventing excessive inflammatory responses that can lead to chronic inflammatory diseases.

Protein Structure

SIGIRR is characterized by the following structural components:

• Extracellular Domain: Contains a single immunoglobulin (Ig)-like domain, which is atypical compared to other members of the IL-1R family that usually have three Ig-like domains.
• Transmembrane Domain: A single-pass transmembrane region that anchors the receptor in the cell membrane.
• Intracellular Domain: Features a Toll/IL-1 receptor (TIR) domain, which is crucial for its signaling functions. However, unlike other TIR-containing receptors, SIGIRR's TIR domain has unique structural motifs that confer its inhibitory functions.

Classification and Subtypes

SIGIRR is classified under the IL-1 receptor family and is often grouped with TLRs due to its involvement in regulating their signaling pathways. It does not have distinct subtypes but is often studied in the context of its interactions with various TLRs and IL-1Rs.

Function and Biological Significance

SIGIRR serves several critical roles in immune regulation:

• Negative Regulation of TLR and IL-1R Signaling: SIGIRR inhibits signaling pathways triggered by TLRs and IL-1Rs, reducing the production of pro-inflammatory cytokines such as IL-1, IL-6, and TNF-α.
• Prevention of Excessive Inflammation: By dampening TLR and IL-1R signaling, SIGIRR prevents excessive inflammatory responses that can lead to tissue damage and chronic inflammatory conditions.
• Immune Homeostasis: Maintains a balance between immune activation and suppression, ensuring that the immune response is proportionate to the threat.
• Epithelial Barrier Protection: In epithelial tissues, SIGIRR helps protect against inflammation-induced damage, maintaining the integrity of barriers such as the intestinal lining.

Clinical Issues

Alterations in SIGIRR expression or function are associated with several pathological conditions:

• Chronic Inflammatory Diseases: Reduced SIGIRR expression or function can lead to uncontrolled inflammation, contributing to diseases such as inflammatory bowel disease (IBD), rheumatoid arthritis, and asthma.
• Infections: While SIGIRR’s inhibitory role is protective against chronic inflammation, its overexpression or hyperactivity may impair effective immune responses against infections, making individuals more susceptible to bacterial and viral pathogens.
• Cancer: Dysregulation of SIGIRR can influence tumor development and progression, as chronic inflammation is a known factor in carcinogenesis.

Summary

Single Immunoglobulin Interleukin-1 Related Receptor (SIGIRR) is a critical negative regulator of TLR and IL-1R signaling pathways. Structurally, it features a unique single Ig-like extracellular domain, a transmembrane region, and an intracellular TIR domain tailored for inhibitory functions. SIGIRR is essential for controlling inflammation and maintaining immune homeostasis, protecting against chronic inflammatory diseases while balancing effective immune responses. Understanding SIGIRR's regulatory mechanisms offers valuable insights into potential therapeutic targets for treating inflammatory and autoimmune diseases, infections, and cancer.