"IL-36" redirects here. For the road formerly known as Illinois Route 36, seeIllinois Route 94.
Interleukin 36, orIL-36, is a group ofcytokines in theIL-1 family withpro-inflammatory effects. The role of IL-36 in inflammatory diseases is under investigation.[1]
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.[2]IL36A,IL36B, andIL36G are IL-36 receptoragonists.IL36RA is an IL-36 receptorantagonist, inhibiting IL-36R signaling. The agonists are known to activateNF-κB,mitogen-activated protein kinases, Erk1/2 andJNK through IL-36R/IL-1RAcP, which targets theIL-8 promotor and results inIL-6 secretion and induces various proinflammatory mediators.[3][4] Binding of the IL-36R agonists to IL-1Rrp2 recruitsIL-1RAcP, activating the signaling pathway. IL-36Ra binds to IL-36R, preventing the recruitment of IL-1RAcP.[1]
IL-36 has been found to activateT cell proliferation and release ofIL-2.[5] 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.[6]
The genes encoding for the IL-36 cytokines are found onchromosome 2q14.1.[8][9][10] All three are located in acluster with other members ofIL-1 family and the gene order fromcentromere totelomere isIL-1A-IL-1B-IL-37-IL-36G-IL-36A-IL-36B-IL-36RN-IL1F10-IL-1RN, and onlyIL-1A,IL-1B andIL-36B.[11] All of them probably arose from a common ancestral gene, which is most likely a primordialIL-1 receptor antagonist gene.[12]
All three genes are mainly expressed in keratinocytes, bronchial epithelium, brain tissue, and monocytes/macrophages.[6] In the epidermis IL-36 cytokine expression is limited to granular layer keratinocytes with little to no expression in basal layer keratinocytes.[13]
IL-36Ra is constitutively expressed in keratinocytes, whereas IL-36γ expression in keratinocytes is rapidly induced after stimulation withTNF or PMA (Phorbol 12-myristate 13-acetate).[14]
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 bothhepatocellular carcinoma andcolorectal cancer patients.[6]
Studies revealed that T cells were sufficient to cause skin inflammation afterStaphylococcus aureus exposure on mice, mediating the skin inflammation via IL-36-controlled,IL-17-dependent T cell responses.[16]
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 usefulbiomarkers in patients with psoriasis.[17]
^abcdeGresnigt MS, van de Veerdonk FL (December 2013). "Biology of IL-36 cytokines and their role in disease".Seminars in Immunology.25 (6):458–65.doi:10.1016/j.smim.2013.11.003.PMID24355486.
