The interleukin-1 receptor family

Semin Immunol. 2013 Dec 15;25(6):394-407. doi: 10.1016/j.smim.2013.10.023. Epub 2013 Nov 15.


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.

Keywords: IL-1 receptors; IL-1R family; Inflammation; Interleukin-1; Resolution.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptive Immunity
  • Humans
  • Inflammation / immunology*
  • Interleukin-1 / immunology
  • Receptors, Interleukin-1 / genetics
  • Receptors, Interleukin-1 / immunology*
  • Receptors, Interleukin-1 / ultrastructure*
  • Signal Transduction / immunology
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / immunology


  • Interleukin-1
  • Receptors, Interleukin-1
  • Toll-Like Receptors