New insights on IL‑36 in intestinal inflammation and colorectal cancer (Review)

Abstract

Interleukin (IL)-36 is a member of the IL-1 superfamily, which includes three receptor agonists and one antagonist and exhibits a familial feature of inflammatory regulation. Distributed among various tissues, such as the skin, lung, gut and joints, the mechanism of IL-36 has been most completely investigated in the skin and has been used in clinical treatment of generalized pustular psoriasis. Meanwhile, the role of IL-36 in the intestine has also been under scrutiny and has been shown to be involved in the regulation of various intestinal diseases. Inflammatory bowel disease and colorectal cancer are the most predominant inflammatory and neoplastic diseases of the intestine, and multiple studies have identified a complex role for IL-36 in both of them. Indeed, inhibiting IL-36 signaling is currently regarded as a promising therapeutic approach. Therefore, the present review briefly describes the composition and expression of IL-36 and focuses on the role of IL-36 in intestinal inflammation and colorectal cancer. The targeted therapies that are currently being developed for the IL-36 receptor are also discussed.

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“…IL-36’s role in fibrosis development is largely described in organs other than the gut, such as the lung, skin, kidney, and heart [ 81 , 82 ]. In the last few years, its involvement in bowel diseases has also been hypothesized [ 83 ]. Scheibe et al analyzed the expression of IL-36 and its receptor (IL-36R) in intestinal tissue samples from patients with IBD (92 with CD and 48 with UC) compared to controls.…”

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“…and Sharma and Kanneganti 195 , 197 IL-36α, IL-36β, IL-36γ activated monocytes, macrophages, and keratinocytes produce a variety of pro-inflammatory factors to stimulate T cells together keratinocytes, other barrier tissues, neutrophils Li et al., Li et al., and Xu et al. 195 , 198 , 199 IL-37 anti-inflammatory effect monocytes, macrophages, epithelial cells, activated B cells Li et al. 195 IL-38 N terminus of apoptotic cells Li et al.…”