IL-36

Full name: Interleukin-36

Family:1,2 Composed of IL-36α, IL-36β, IL-36γ, and IL-36Ra. These IL-36 cytokines in turn belong to the IL-1 superfamily (IL-1α, IL-1β, IL-18, and IL-33)

Receptors:1 IL-36Ra

Major cellular sources:1 Internal endothelial tissues, skin, and bone marrow–derived macrophages

Major cellular targets:1 Keratinocytes and other epithelial barriers; at lower levels on DCs, naïve CD4+ T cells, differentiated Th1 and Th2 cells; very low levels on Th17 cells

Disease states associated with:1,2 Psoriasis, asthma, rheumatoid arthritis, inflammatory bowel disease

Major physiologic functions:

  • IL-36 regulates the function of both nonimmune and immune cells.2

  • IL-36 can be regulated by different inflammatory components (such as IL-22, IL-17A, TNF-α, and IFN-γ) and cells (such as keratinocytes).2

  • Additionally, IL-36 is a common mediator of innate and adaptive immune responses and promotes an early inflammatory response to tissue injury or infection.1

  • By signaling through the MAPK and NF-κB pathway, IL-36 induces the production of pro-inflammatory cytokines, thereby exerting a pro-inflammatory effect.1,2

  • IL-36Ra is a natural inhibitor of IL-36R and has anti-inflammatory biological effects on immune cells.1,3

  • IL-36 mediates lesional psoriasis skin, dermal, and epidermal inflammation and keratinocyte proliferation.3

  • IL-36 can be induced by Th17 cytokines and directly regulates IL-8 and IL-6. It also regulates the expression and enhances the function of Th17.3

DC: dendritic cell; IFN: interferon; IL: interleukin; IL-36R: IL-36 receptor; IL-36Ra: IL-36R antagonist; MAPK: mitogen-activated protein kinase; NF-κB: nuclear factor-kappa B; Th: T helper; TNF: tumor necrosis factor.

References:

  • 1.

    Akdis M, Aab A, Altunbulakli C, et al. J Allergy Clin Immunol. 2016;138:984-1010.

  • 2.

    Yuan ZC, Xu WD, Liu XY, et al. Front Immunol. 2019;10:2532.

  • 3.

    Shaik Y, Sabatino G, Maccauro G, et al. Int J Immunopathol Pharmacol. 2013;26:27-36.