IL36G

Expression

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

Function

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. 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). 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. As with many other interleukin-1 family cytokines IL-36γ requires proteolytic cleavage of its N-terminus for full biological activity. 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.

References

References

1. (June 2000). "Identification and gene organization of three novel members of the IL-1 family on human chromosome 2". Genomics.
2. (April 2000). "Identification and initial characterization of four novel members of the interleukin-1 family". The Journal of Biological Chemistry.
3. (May 2002). "A sequence-based map of the nine genes of the human interleukin-1 cluster". Genomics.
4. (May 2002). "Genomic organization of the interleukin-1 locus". Genomics.
5. (2019). "Biology of IL-36 Signaling and Its Role in Systemic Inflammatory Diseases". Frontiers in Immunology.
6. (August 2022). "Proprotein convertase subtilisin/kexin type 9 is a psoriasis-susceptibility locus that is negatively related to IL36G". JCI Insight.
7. (December 2013). "The interleukin-1 family: back to the future". Immunity.
8. (April 2015). "Regulation and function of interleukin-36 cytokines in homeostasis and pathological conditions". Journal of Leukocyte Biology.
9. (September 2018). "Detection of IL-36γ through noninvasive tape stripping reliably discriminates psoriasis from atopic eczema". The Journal of Allergy and Clinical Immunology.
10. (April 2015). "IL-36γ (IL-1F9) is a biomarker for psoriasis skin lesions". The Journal of Investigative Dermatology.
11. (December 2011). "Interleukin-36 (IL-36) ligands require processing for full agonist (IL-36α, IL-36β, and IL-36γ) or antagonist (IL-36Ra) activity". The Journal of Biological Chemistry.
12. (March 2017). "Cathepsin S is the major activator of the psoriasis-associated proinflammatory cytokine IL-36γ". Proceedings of the National Academy of Sciences of the United States of America.
13. (December 2020). "The Proinflammatory Cytokine IL-36γ Is a Global Discriminator of Harmless Microbes and Invasive Pathogens within Epithelial Tissues". Cell Reports.