1. Academic Validation
  2. The family of the interleukin-1 receptors

The family of the interleukin-1 receptors

  • Immunol Rev. 2018 Jan;281(1):197-232. doi: 10.1111/imr.12606.
Diana Boraschi 1 Paola Italiani 1 Sabrina Weil 2 Michael U Martin 2
Affiliations

Affiliations

  • 1 Institute of Protein Biochemistry, National Research Council, Naples, Italy.
  • 2 Immunology FB08, Justus-Liebig-Universitat Giessen, Giessen, Germany.
Abstract

The extracellular forms of the IL-1 cytokines are active through binding to specific receptors on the surface of target cells. IL-1 ligands bind to the extracellular portion of their ligand-binding receptor chain. For signaling to take place, a non-binding accessory chain is recruited into a heterotrimeric complex. The intracellular approximation of the Toll-IL-1-receptor (TIR) domains of the 2 receptor chains is the event that initiates signaling. The family of IL-1 receptors (IL-1R) includes 10 structurally related members, and the distantly related soluble protein IL-18BP that acts as inhibitor of the cytokine IL-18. Over the years the receptors of the IL-1 family have been known with many different names, with significant confusion. Thus, we will use here a recently proposed unifying nomenclature. The family includes several ligand-binding chains (IL-1R1, IL-1R2, IL-1R4, IL-1R5, and IL-1R6), 2 types of accessory chains (IL-1R3, IL-1R7), molecules that act as inhibitors of signaling (IL-1R2, IL-1R8, IL-18BP), and 2 orphan receptors (IL-1R9, IL-1R10). In this review, we will examine how the receptors of the IL-1 family regulate the inflammatory and anti-inflammatory functions of the IL-1 cytokines and are, more at large, involved in modulating defensive and pathological innate immunity and inflammation. Regulation of the IL-1/IL-1R system in the brain will be also described, as an example of the peculiarities of organ-specific modulation of inflammation.

Keywords

IL-1 receptors; IL-1R family; inflammation; interleukin-1; resolution.

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