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 and mitogen-activated protein kinases to induce various proinflammatory mediators. Binding of the IL-36R agonists to IL-1Rp2 recruits IL-1RAcP, activating the signaling pathway. IL-36Ra binds to IL-36R, preventing the recruitment of IL-1RAcP.
It 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. The genes encoding for the IL-36 cytokines are found on chromosome 2q13.
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, but the enzyme responsible for this is not known.
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