IL36G
Description
The IL36G (interleukin 36 gamma) is a protein-coding gene located on chromosome 2.
Interleukin-36 gamma (IL36G), previously known as interleukin-1 family member 9 (IL1F9), is a protein encoded by the IL36G gene in humans. IL36G is expressed in the epithelium of the skin, gut, and lung, with a predominant expression in the epidermal granular layer keratinocytes of the skin and little to no expression in basal layer keratinocytes. It belongs to the interleukin-1 cytokine family and forms a cytokine gene cluster on chromosome 2 with eight other interleukin-1 family genes. IL36G's activity is mediated by the interleukin-1 receptor-like 2 (IL1RL2/IL1R-rp2/IL-36 receptor) and is specifically inhibited by the interleukin-36 receptor antagonist (IL-36RA/IL1F5/IL-1 delta). Interferon-gamma, tumor necrosis factor-alpha, and interleukin-1β (IL-1β) are known to stimulate the expression of IL36G in keratinocytes. Additionally, IL36G expression in keratinocytes can be induced by multiple pathogen-associated molecular patterns (PAMPs). Both IL-36γ mRNA and protein have been associated with psoriasis lesions and used as biomarkers to differentiate between eczema and psoriasis. Similar to other interleukin-1 family cytokines, IL-36γ requires proteolytic cleavage of its N-terminus for full biological activity.
IL36G, also known as IL1F9, is a cytokine that binds to and signals through the IL1RL2/IL-36R receptor, activating NF-kappa-B and MAPK signaling pathways in target cells. This cytokine is part of the IL-36 signaling system, which is thought to be present in epithelial barriers and involved in local inflammatory responses. It shares the coreceptor IL1RAP with the IL-1 system. IL36G has been implicated in skin inflammatory responses, acting on keratinocytes, dendritic cells, and indirectly on T-cells to drive tissue infiltration, cell maturation, and cell proliferation. In cultured keratinocytes, it induces the expression of macrophage, T-cell, and neutrophil chemokines such as CCL3, CCL4, CCL5, CCL2, CCL17, CCL22, CCL20, CXCL8, and CXCL1. Additionally, IL36G stimulates its own expression and that of prototypic cutaneous pro-inflammatory parameters like TNF-alpha, S100A7/psoriasin, and inducible NOS. This cytokine may play a role in pro-inflammatory responses during neutrophilic airway inflammation, activating mitogen-activated protein kinases and NF-kappa B in primary lung fibroblasts and stimulating the expression of IL-8, CXCL3, and the Th17 chemokine CCL20 in lung fibroblasts. IL36G might also be involved in the innate immune response to fungal pathogens, such as Aspergillus fumigatus.
IL36G is also known as IL-1F9, IL-1H1, IL-1RP2, IL1E, IL1F9, IL1H1, IL1RP2.
