98%
921
2 minutes
20
SIGIRR, also known as the single immunoglobulin interleukin-1 receptor (IL-1R)-related molecule, is a member of the IL-1 receptor superfamily and is believed to play a pivotal role in inflammation and anti-inflammatory regulation within the body. Studies have shown that SIGIRR expression is associated with autoimmunity, inflammatory disorders, graft rejection, viral infection, thrombosis and tumour progression. Due to its unique structure and function, SIGIRR is commonly referred to as an 'orphan receptor', with IL-37 being the only confirmed ligand molecule for SIGIRR to date. The primary mechanism through which SIGIRR exerts its anti-inflammatory regulatory effect involves the negative modulation of the Toll-like receptor-IL-1R (TLR-IL-1R) signalling pathway. TLR-IL-1R signalling plays critical roles in immune responses triggered by microbial invasion and alterations in the tumour immune microenvironment. This article provides an overview of research findings on SIGIRR as an orphan receptor and its regulatory role in maintaining a delicate balance between natural immune activation and uncontrolled inflammatory processes under pathological conditions.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12315662 | PMC |
http://dx.doi.org/10.1017/erm.2025.10009 | DOI Listing |
Expert Rev Mol Med
June 2025
Department of Hepatology, First Hospital of Jilin University, Changchun, Jilin, P.R. China.
SIGIRR, also known as the single immunoglobulin interleukin-1 receptor (IL-1R)-related molecule, is a member of the IL-1 receptor superfamily and is believed to play a pivotal role in inflammation and anti-inflammatory regulation within the body. Studies have shown that SIGIRR expression is associated with autoimmunity, inflammatory disorders, graft rejection, viral infection, thrombosis and tumour progression. Due to its unique structure and function, SIGIRR is commonly referred to as an 'orphan receptor', with IL-37 being the only confirmed ligand molecule for SIGIRR to date.
View Article and Find Full Text PDFCytokine
October 2019
Center for Cardiovascular Research, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, United States; Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia. Electronic address:
IL-37 is a member of the IL-1 family, but unlike most other members of this family of cytokines, it has wide-ranging anti-inflammatory properties. Initially shown to bind IL-18 binding protein and prevent IL-18-mediated inflammation, its known role has been expanded to include distinct pathways, both intracellular involving the transcription factor Smad3, and extracellular via binding to the orphan receptor IL-1R8. A number of recent publications investigating the role of IL-37 in atherosclerosis and ischemic heart disease have revealed promising therapeutic value of the cytokine.
View Article and Find Full Text PDFJ Leukoc Biol
February 2017
Laboratory of Innate Immunity, Ste-Justine Research Center, Université de Montréal, Montreal, Quebec, Canada;
IL-37 is a cytokine belonging to the IL-1 family. Although discovered in silico in 2000, significant advances in the understanding of its biology were made only in recent years. It is a member of the family with potent anti-inflammatory and immunosuppressive properties.
View Article and Find Full Text PDFEur J Immunol
May 2016
Ludwig-Maximilian-University, Munich, Germany.
IL-37 is unique in the IL-1 family in that unlike other members of the family, IL-37 broadly suppresses innate immunity. IL-37 can be elevated in humans with inflammatory and autoimmune diseases where it likely functions to limit inflammation. Transgenic mice expressing human IL-37 (IL37-tg) exhibit less severe inflammation in models of endotoxin shock, colitis, myocardial infarction, lung, and spinal cord injury.
View Article and Find Full Text PDFNat Immunol
April 2015
1] Ritchie Centre, MIMR-PHI Institute of Medical Research, Melbourne, Victoria, Australia. [2] Department of Paediatrics, Monash University, Melbourne, Australia. [3] Department of Medicine, University of Colorado Denver, Aurora, Colorado, USA.
Interleukin 37 (IL-37) and IL-1R8 (SIGIRR or TIR8) are anti-inflammatory orphan members of the IL-1 ligand family and IL-1 receptor family, respectively. Here we demonstrate formation and function of the endogenous ligand-receptor complex IL-37-IL-1R8-IL-18Rα. The tripartite complex assembled rapidly on the surface of peripheral blood mononuclear cells upon stimulation with lipopolysaccharide.
View Article and Find Full Text PDF