IL36G

IL36G is well-expressed in the epithelium of the skin, gut, and lung.^[9] In the skin IL36G is predominantly expressed in epidermal granular layer keratinocytes with little to no expression in basal layer keratinocytes.^[10]

The protein encoded by this gene is a member of the interleukin-1 cytokine family. This gene and eight other interleukin-1 family genes form a cytokine gene cluster on chromosome 2.^[11] The activity of this cytokine is mediated via the interleukin-1 receptor-like 2 (IL1RL2/IL1R-rp2/IL-36 receptor), and is specifically inhibited by interleukin-36 receptor antagonist, (IL-36RA/IL1F5/IL-1 delta). Interferon-gamma, tumor necrosis factor-alpha and interleukin-1 β (IL-1β) are reported to stimulate the expression of this cytokine in keratinocytes. The expression of this cytokine in keratinocytes can also be induced by a multiple Pathogen-Associated Molecular Patterns (PAMPs).^[12] Both IL-36γ mRNA and protein have been linked to psoriasis lesions and has been used as a biomarker for differentiating between eczema and psoriasis.^[13][14] As with many other interleukin-1 family cytokines IL-36γ requires proteolytic cleavage of its N-terminus for full biological activity.^[15] However, unlike IL-1β the activation of IL-36γ is inflammasome-independent. IL-36γ is specifically cleaved by the endogenous protease cathepsin S as well exogenous proteases derived from fungal and bacterial pathogens.^[16][17]