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Psoriasis is an immune-mediated inflammatory skin disease that involves mainly T helper (Th)17, Th1 and Th22 lymphocytes, which cause hyper-proliferation of the epidermis with aberrant differentiation of keratinocytes, and local production of chemokines and cytokines. These fuel a self-amplifying loop where these products act on T cells to perpetuate cutaneous inflammatory processes. Among the various inflammatory mediators involved, interleukin (IL)-36 cytokines are important for the recruitment and activation of neutrophils and Th17 cells in psoriatic skin. In particular, IL-36s induce chemokines and cytokines interfere with differentiation/cornification programs in the epidermis, as well as promote pathological angiogenesis and endothelial cell activation. IL-36 cytokines belong to the IL-1 family, and comprise IL-36α, IL-36β, and IL-36γ agonists as well as IL-36 receptor antagonist and IL-38 antagonists. IL-36 cytokines are up-regulated in psoriatic epidermis, and their expression is strongly induced by TNF-α and IL-17. Contrarily, IL-38 antagonist is downregulated, and its impaired expression may be relevant to the dysregulated inflammatory processes induced by IL-36. Here, we discuss on the pathogenic mechanisms leading to the altered balance of IL-36 agonists/antagonists and the significance of this dysregulation in psoriasis. Collection of the information will provide a theoretical basis for the development of novel therapeutic strategies based on IL-36 agonist/antagonist manipulation in psoriasis.
Madonna et al. (Fri,) studied this question.