IL1RL1 - Interleukin 1 Receptor Like Protein 1 | Elisa - Clia - Antibody - Protein

Background

Interleukin 1 Receptor-Like Protein 1 (IL1RL1), also known as ST2, is a member of the interleukin-1 receptor family. It plays a significant role in the immune response by mediating the effects of the cytokine IL-33. IL1RL1 is expressed in various cell types, including immune cells such as T cells, mast cells, and macrophages, as well as non-immune cells like fibroblasts and epithelial cells. The interaction between IL1RL1 and IL-33 is critical in promoting Th2 immune responses, which are involved in allergic reactions and protection against parasitic infections. IL1RL1 has two main isoforms: a membrane-bound form (ST2L) and a soluble form (sST2), each playing distinct roles in immune regulation.

Protein Structure

IL1RL1 is a type I transmembrane protein composed of several structural domains:

• Extracellular Domain: Contains three immunoglobulin (Ig)-like domains that are crucial for binding IL-33.
• Transmembrane Domain: A single-pass transmembrane helix that anchors the receptor in the cell membrane.
• Intracellular Domain: Features Toll/IL-1 receptor (TIR) domains involved in downstream signal transduction through the MyD88 adaptor protein, leading to activation of NF-κB and MAPK pathways.

Classification and Subtypes

IL1RL1 is classified within the IL-1 receptor family and is closely related to other IL-1 receptor family members, including IL1R1 and IL1R2. The main isoforms of IL1RL1 include:

• ST2L (Membrane-bound form): Involved in IL-33 signaling and subsequent immune responses.
• sST2 (Soluble form): Acts as a decoy receptor, binding IL-33 and preventing it from interacting with ST2L, thus regulating the extent of the IL-33-mediated immune response.

Function and Biological Significance

IL1RL1 is integral to several immune functions:

• Th2 Immune Response: IL1RL1, through its interaction with IL-33, promotes the differentiation and function of Th2 cells, which are important for combating parasitic infections and mediating allergic responses.
• Mast Cell Activation: IL1RL1 is expressed on mast cells, where it contributes to their activation and degranulation in response to IL-33, leading to the release of histamines and other mediators involved in allergic reactions.
• Regulation of Inflammation: Both isoforms of IL1RL1 play roles in modulating inflammatory responses. sST2, by sequestering IL-33, helps to limit excessive inflammation.

Clinical Issues

Dysregulation of IL1RL1 signaling is associated with various diseases:

• Allergic Diseases: Elevated levels of IL1RL1 and IL-33 are implicated in allergic diseases such as asthma, atopic dermatitis, and allergic rhinitis.
• Cardiovascular Diseases: Increased sST2 levels are associated with poor outcomes in heart failure and myocardial infarction, serving as a biomarker for these conditions.
• Autoimmune Diseases: IL1RL1 and IL-33 have roles in autoimmune diseases like rheumatoid arthritis, where they contribute to chronic inflammation and tissue damage.

Summary

IL1RL1 (Interleukin 1 Receptor-Like Protein 1) is a crucial receptor in the IL-1 receptor family, mediating the effects of IL-33. Structurally, it comprises extracellular Ig-like domains, a transmembrane region, and an intracellular TIR domain. IL1RL1 is essential for Th2 immune responses, mast cell activation, and regulation of inflammation. Dysregulation of IL1RL1 signaling is implicated in allergic diseases, cardiovascular diseases, and autoimmune conditions. Understanding the roles of IL1RL1 and its isoforms (ST2L and sST2) provides insights into their biological significance and potential as therapeutic targets in various inflammatory and immune-related diseases.