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IL-36 cytokines are primarily expressed in epithelial tissues and are implicated in the pathogenesis of skin diseases, particularly psoriasis, as well as conditions like psoriatic arthritis, systemic lupus erythematosus, and inflammatory bowel disease.
IL-36A signals through the IL1RL2/IL-36R receptor, activating NF-kappa-B and MAPK pathways, leading to a pro-inflammatory response. It influences skin inflammation by acting on keratinocytes and dendritic cells, driving tissue infiltration and cell proliferation. In cultured keratinocytes, IL-36 induces various chemokines (e.g., CCL2, CCL5, CXCL8) and pro-inflammatory cytokines (e.g., TNF-alpha, IL-6). In monocytes, it upregulates IL-1A and IL-1B, while in dendritic cells, it enhances maturation markers like CD83 and CD86, facilitating T-cell proliferation. IL-36 may also contribute to pro-inflammatory effects in the lung.