Regulation and function of interleukin-36 cytokines

Immunol Rev. 2018 Jan;281(1):169-178. doi: 10.1111/imr.12610.

Abstract

The interleukin (IL)-36 cytokines include 3 agonists, IL-36α, IL-36β, and IL-36γ that bind to a common receptor composed of IL-36R and IL-1RAcP to stimulate inflammatory responses. IL-36Ra is a natural antagonist that binds to IL-36R, but does not recruit the co-receptor IL-1RAcP and does not stimulate any intracellular responses. The IL-36 cytokines are expressed predominantly by epithelial cells and act on a number of cells including immune cells, epithelial cells, and fibroblasts. Processing of the N-terminus is required for full agonist or antagonist activity for all IL-36 members. The role of IL-36 has been extensively demonstrated in the skin where it can act on keratinocytes and immune cells to induce a robust inflammatory response that has been implicated in psoriatic disorders. Emerging data also suggest a role for this cytokine family in pulmonary and intestinal physiology and pathology.

Keywords: IL-1 family; inflammation; intestine; lung; psoriasis.

Publication types

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

MeSH terms

  • Animals
  • Arthritis, Psoriatic / immunology*
  • Epithelial Cells / physiology*
  • Fibroblasts / physiology*
  • Humans
  • Inflammation
  • Interleukin-1 / metabolism*
  • Interleukin-1 Receptor Accessory Protein / metabolism
  • Intestines / pathology
  • Intestines / physiology*
  • Protein Binding
  • Receptors, Interleukin / metabolism
  • Skin / metabolism*
  • Skin / pathology

Substances

  • Interleukin-1
  • Interleukin-1 Receptor Accessory Protein
  • Receptors, Interleukin
  • interleukin 36, human
  • interleukin-36 receptor, human