interleukin 36 interleukin 36 interleukin 36, or il-36, is a group of cytokines in the il-1 family with pro-inflammatory effects. the role of il-36 in inflammatory diseases is under investigation. there are four members of the il-36 family which bind to the il-36 receptor (il1rl2/il-1rrp2/il-36 receptor dimer) with varying affinities. 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 activate nf-κb, mitogen-activated protein kinases, erk1/2 and jnk through il-36r/il-1racp, which targets the il-8 promotor and results in il-6 secretion and induces various proinflammatory mediators. binding of the il-36r agonists to il-1rrp2 recruits il-1racp, activating the signaling pathway. il-36ra binds to il-36r, preventing the recruitment of il-1racp. function il-36 has been found to activate t cell proliferation and release of il-2. before the functions of the il-36 cytokines were determined, they were named as derivatives of il-1f; they were renamed to their current designations in 2010. due to their predominant expression in epithelial tissues, 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-36 must be cleaved at the n-terminus to become active, probable enzymes mediating the activation could be neutrophil granule-derived proteases, elastase, and cathepsin g, although they may activate the cytokines differentially. il-36 is expressed by many cells types, most predominantly keratinocytes, respiratory epithelium, various nervous tissue, and monocytes. genes and expression the genes encoding for the il-36 cytokines are found on chromosome 2q14.1. all three are located in a cluster with other members of il-1 family and the gene order from centromere to telomere is il-1a-il-1b-il-37-il-36g-il-36a-il-36b-il-36rn-il1f10-il-1rn, and only il-1a, il-1b and il-36b. all of them probably arose from a common ancestral gene, which is most likely a primordial il-1 receptor antagonist gene. all three 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-36ra is constitutively expressed in keratinocytes, whereas il-36γ expression in keratinocytes is rapidly induced after stimulation with tnf or pma (phorbol 12-myristate 13-acetate). clinical significance il-36-alpha functions primarily in skin and demonstrates increased expression in psoriasis. in addition, 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 regulatory role in the pathogenesis of inflammatory disorders such as folliculitis and eosinophilic pustular folliculitis. in addition, in acute generalized exanthematous pustulosis, il-36 (mainly il-36 gamma) was overexpressed in skin lesions. studies revealed that t cells were sufficient to cause skin inflammation after staphylococcus aureus exposure on mice, mediating the skin inflammation via il-36-controlled, il-17-dependent t cell responses. il-36 is significantly involved in the pathogenesis of psoriasis leading to it being targeted therapeutically. human psoriatic skin plaques displayed elevated il-36beta. in addition, it was found that 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.