Regulation and function of interleukin-36 cytokines in homeostasis and pathological conditions

J Leukoc Biol. 2015 Apr;97(4):645-52. doi: 10.1189/jlb.3RI1014-495R. Epub 2015 Feb 11.


IL-36α, IL-36β, and IL-36γ are members of the IL-1 family of cytokines that signal through a common receptor composed of IL-36R and IL-1R/AcP to activate NF-κB and MAPKs, such as p38 and JNK, and promote inflammatory responses. IL-36Ra is a natural antagonist of the 3 IL-36 agonists that binds to IL-36R and inhibits binding of the agonistic ligands. These 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 demonstrated extensively in the skin, where it can act on keratinocytes and immune cells to induce a robust inflammatory response and is implicated strongly through functional and genetic evidence in the pathology of psoriatic disorders. Emerging data also suggest a role for this cytokine family in pulmonary physiology and pathology. Although much has been learned about the biochemistry of IL-36 and its role in various tissues, it is clear that we are at an early stage in our understanding of the full biology of these cytokines.

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

Publication types

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

MeSH terms

  • Animals
  • Chromosomes, Human, Pair 2 / genetics
  • Dendritic Cells / immunology
  • Epithelial Cells / immunology
  • Humans
  • Inflammation / physiopathology*
  • Interleukin-1 / agonists
  • Interleukin-1 / genetics
  • Interleukin-1 / immunology
  • Interleukin-1 / physiology*
  • Interleukin-1 Receptor Accessory Protein / physiology
  • Lung / cytology
  • Lung / immunology
  • Lung / metabolism
  • Lymphocyte Subsets / immunology
  • MAP Kinase Signaling System
  • Mice
  • Multigene Family
  • NF-kappa B / metabolism
  • Organ Specificity
  • Protein Processing, Post-Translational
  • Psoriasis / physiopathology
  • Receptors, Interleukin / chemistry
  • Receptors, Interleukin / physiology*
  • Signal Transduction / physiology*
  • Skin / cytology
  • Skin / immunology
  • Skin / metabolism


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