Interleukin-36 gamma previously known as interleukin-1 family member 9 (IL1F9) is a protein that in humans is encoded by the IL36G gene.[5][6][7][8]
Interleukin-36 gamma previously known as interleukin-1 family member 9 (IL1F9) is a protein that in humans is encoded by the IL36G gene.[5][6][7][8]
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]