MOLECULES

Full name: Interleukin-36

Family: 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)^1,2

Receptors: IL-36Ra¹

Major cellular sources: Internal endothelial tissues, skin, and bone marrow–derived macrophages¹

Major cellular targets: Keratinocytes and other epithelial barriers; at lower levels on DCs, naïve CD4+ T cells, differentiated Th1 and Th2 cells; very low levels on Th17 cells¹

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

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- , and IFN- ) 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-KB 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- B: nuclear factor-kappa B; Th: T helper; TNF: tumor necrosis factor.