The interleukin-1 receptor family.
The activity of each member of the IL-1 family of ligands is mediated by its own receptor. Each ligand binds specifically to the extracellular "ligand binding chain" containing three Ig-like regions. With the exception of the IL-1 and IL-36 receptor antagonists, a second chain, termed the "accessory chain", is recruited, forms a heterotrimetic complex with the ligand binding chain and the ligand, and signal transduction is initiated. Each ligand binding or accessory chain shares a common cytosolic segment termed the Toll-IL-1-receptor (TIR) domain. Another family of 13 receptors, termed Toll-like receptors (TLR), have extracellular leucine-rich repeat domains, which bind a broad spectrum of microbial products. All TLR share a nearly identical TIR domain with all members of the IL-1 receptor family. Hence signal transduction and the biological consequences of TLR ligands and IL-1 family ligands are often the same and both receptor families contribute to innate inflammation and host defense. The IL-1 family of receptors is comprised of ten distinct but related gene products. The receptors are indicated by the term IL-1 receptor (IL-1R) followed by a numeral, assigned chronologically by discovery, for example, IL-1R1, IL-1R2, IL-1R3, etc. The ligand binding chain for IL-1α and IL-1β is IL-1R1 and the accessory chain is IL-1R3. IL-1α, IL-1β, IL-33 and IL-36 use IL-1R3 as their accessory chain. IL-1R2 is a non-signalling "decoy" receptor that sequesters the IL-1β and IL-1R3. IL-1R8 exhibits anti-inflammatory properties by reducing IL-1 and TLR signalling. Presently there are two orphan receptors, IL-1R9 and IL-1R10, which have no known function. This review examines the characteristics and functional roles of the IL-1R family in the regulation of innate inflammation, host defense and acquired immunity.
Institute of Protein Biochemistry, National Research Council, Via Pietro Castellino 111, 80131 Naples, Italy. Electronic address: diana.boraschi@gmail.com.
Diana
D
Boraschi
ALTA S.r.l., Via Fiorentina 151, 56100 Siena, Italy. Electronic address: aldo.tagliabue@gmail.com.
Aldo
A
Tagliabue
D056704:Adaptive Immunity; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D007375:Interleukin-1 / Q000276:immunology; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000276:immunology* / Q000648:ultrastructure*; D015398:Signal Transduction / Q000276:immunology; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology
D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D051193:Toll-Like Receptors
IL-1 receptors; IL-1R family; Inflammation; Interleukin-1; Resolution