Interleukin-1 Receptor Accessory Protein (IL1RAP) is a protein that plays an important role in cellular communication and immune responses. It participates in various signaling pathways, helping the body manage inflammation and other physiological processes. Its widespread presence throughout the body highlights its importance in maintaining cellular functions.
Understanding IL1RAP
IL1RAP is an accessory protein that assists primary receptors in forming functional complexes. It does not directly bind signaling molecules but partners with receptors like the Interleukin-1 receptor (IL-1R1) to enable signal transmission into the cell. IL1RAP is found on the surface of various cells, including those in the liver, placenta, blood, and specific immune cells like monocytes.
Its structure includes an extracellular domain, a transmembrane domain, and an intracellular domain. These parts allow IL1RAP to interact with external signals and internal cellular machinery. The gene encoding IL1RAP is located on chromosome 3 in humans.
How IL1RAP Functions in the Body
IL1RAP is a co-receptor in the signaling pathways of the interleukin-1 (IL-1) family of cytokines, including IL-1α, IL-1β, IL-33, and IL-36. These cytokines mediate inflammation and immune responses. IL1RAP forms a complex with primary receptors, such as IL-1R1 for IL-1 or ST2 for IL-33, to receive signals.
When a cytokine like IL-1 binds to its primary receptor, IL1RAP is recruited to form an active signaling complex on the cell membrane. This assembly initiates a cascade of events inside the cell. It activates downstream signaling molecules like IL-1R-associated kinases (IRAKs) and tumor necrosis factor receptor-associated factor 6 (TRAF6). This activation leads to cellular responses, including inflammatory processes or immune cell activation.
IL1RAP’s Involvement in Disease
Dysregulation or abnormal activity of IL1RAP can contribute to various diseases. Its overactivity is linked to inflammatory and autoimmune conditions. For instance, in diseases such as rheumatoid arthritis, systemic lupus erythematosus, and inflammatory bowel disease, excessive IL1RAP signaling can lead to sustained inflammatory responses.
IL1RAP also has an emerging role in certain cancers, promoting disease progression. It is overexpressed in various cancer types, including acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and breast cancer. In these contexts, IL1RAP can contribute to tumor growth by promoting inflammatory signals and cell proliferation. Its pathways are also implicated in neuroinflammatory and neurodegenerative diseases like Alzheimer’s and Parkinson’s.
Therapeutic Strategies Targeting IL1RAP
Research is exploring therapeutic approaches to modulate IL1RAP activity. Targeting IL1RAP is a promising strategy because it can block harmful inflammatory signals without completely shutting down other immune functions. This selective targeting offers a precise way to manage diseases driven by excessive inflammation.
Potential treatments include monoclonal antibodies that block IL1RAP. For example, nidanilimab (CAN04), an anti-IL1RAP monoclonal antibody, is being evaluated in clinical trials for solid malignant tumors. MAB-hR3, another antagonistic monoclonal antibody, is a broad-spectrum anti-inflammatory agent for autoimmune and inflammatory diseases. These therapies aim to interfere with IL1RAP’s ability to form signaling complexes, preventing the activation of downstream inflammatory pathways.