Interleukin 36, or IL-36, is a group of cytokines in the IL-1 family with pro-inflammatory effects.
There are four members of the IL-36 family which bind to the IL-36 receptor: IL36A, IL36B, and IL36G are IL-36 receptor agonists.
IL36RA is an IL-36 receptor antagonist, inhibiting IL-36R signaling.
The agonists are known to activates and targets the IL-8 promotor and results in IL-6 secretion and induces various proinflammatory mediators.
IL-36 has been found to activate T cell proliferation and release of IL-2.
IL_36 has predominant expression in epithelial tissues, and IL-36 cytokines are believed to play a significant role in the pathogenesis of skin diseases, especially that of psoriasis.
IL-36 has also been linked to psoriatic arthritis, systemic lupus erythematosus, inflammatory bowel disease, ulcerative colitis, Crohn’s disease, and Sjögren’s syndrome.
IL-36α is expressed in spleen, lymph nodes, tonsils, bone marrow, B-cells, and T lymphocytes.
IL-36β is expressed in the tonsils, bone marrow, heart, placenta, lung, testes, intestine, monocytes and B-lymphocytes.
IL-36ra is highly expressed by keratinocytes, in psoriatic skin, placenta, uterus, brain, kidneys, monocytes, B-lymphocytes and dendritic cells.
IL-36ra acts as a non-specific inhibitor of inflammation and innate immunity. It inhibits IL-36α induced NF-κB activation.
Expression is increased during chronic contact hypersensitivity, herpes zoster.
IL-36ra is highly expressed by keratinocytes, in psoriatic skin, placenta, uterus, brain, kidneys, monocytes, B-lymphocytes and dendritic cells.
IL-36ra shares with IL-1ra 52% homology in the amino acid sequence.
IL-36ra acts as a non-specific inhibitor of inflammation and innate immunity.
IL-36 must be cleaved at the N-terminus to become active.
IL-36 is expressed by many cells types, most predominantly keratinocytes, respiratory epithelium, various nervous tissue, and monocytes.
The genes encoding for the IL-36 cytokines are found on chromosome 2.
Genes are mainly expressed in keratinocytes, bronchial epithelium, brain tissue, and monocytes/macrophages.
In the epidermis IL-36 cytokine expression is limited to granular layer keratinocytes with little to no expression in basal layer keratinocytes.
IL-36-alpha functions primarily in skin and demonstrates increased expression in psoriasis.
Decreased expression of this gene has been linked to a poor prognosis in both hepatocellular carcinoma and colorectal cancer patients.
IL-36 cytokines may play a role in the pathogenesis of inflammatory disorders such as folliculitis, eosinophilic pustular folliculitis, and acute generalized exanthematous pustulosis.
IL-36 is significantly involved in the pathogenesis of psoriasis, as
psoriatic skin plaques display elevated IL-36beta.
serum IL-36 levels are higher in patients with psoriasis vulgaris and its levels positively correlate with disease activity, suggesting that serum IL-36 levels might serve as useful biomarkers in patients with psoriasis.