IL-36 cytokines and gut immunity

Immunology. 2021 Jun;163(2):145-154. doi: 10.1111/imm.13310. Epub 2021 Feb 24.

Abstract

Interleukin 36 (IL-36) constitutes a group of cytokines that belong to the IL-1 superfamily. Emerging evidence has suggested a role of IL-36 in the pathogenesis of many inflammatory disorders. Intriguingly, in the gastrointestinal tract, IL-36 has a rather complex function. IL-36 receptor ligands are overexpressed in both animal colitis models and human IBD patients and may play both pathogenic and protective roles, depending on the context. IL-36 cytokines comprise three receptor agonists: IL-36α, IL-36β and IL-36γ, and two receptor antagonists: IL-36Ra and IL-38. All IL-36 receptor agonists bind to the IL-36R complex and exert pleiotropic effects during inflammatory settings. Here, we first briefly review the processing and secretion of IL-36 cytokines. We then focus on the current understanding of the immunology effects of IL-36 in gut immunity. In addition, we also discuss the ongoing trials that aim to blockage IL-36R signalling for treating chronic intestinal inflammation and present some unexplored questions regarding IL-36 research.

Keywords: cytokine; inflammatory bowel diseases; interleukin; intestinal inflammation.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Colitis / immunology*
  • Disease Models, Animal
  • Humans
  • Inflammation / immunology*
  • Inflammatory Bowel Diseases / immunology*
  • Interleukin-1 / metabolism*
  • Interleukins / metabolism
  • Intestinal Mucosa / immunology*
  • Molecular Targeted Therapy
  • Receptors, Interleukin-1 / metabolism
  • Signal Transduction

Substances

  • IL1RL2 protein, human
  • IL36RN protein, human
  • Interleukin-1
  • Interleukins
  • Receptors, Interleukin-1
  • interleukin 36, human