Abstract
The excellent clinical efficacy of anti-interleukin 17A (IL-17A) biologics on psoriasis indicates a crucial pathogenic role of IL-17A in this autoinflammatory skin disease. IL-17A accelerates the proliferation of epidermal keratinocytes. Keratinocytes produce a myriad of antimicrobial peptides and chemokines, such as CXCL1, CXCL2, CXCL8, and CCL20. Antimicrobial peptides enhance skin inflammation. IL-17A is capable of upregulating the production of these chemokines and antimicrobial peptides in keratinocytes. CXCL1, CXCL2, and CXCL8 recruit neutrophils and CCL20 chemoattracts IL-17A-producing CCR6+ immune cells, which further contributes to forming an IL-17A-rich milieu. This feed-forward pathogenic process results in characteristic histopathological features, such as epidermal hyperproliferation, intraepidermal neutrophilic microabscess, and dermal CCR6+ cell infiltration. In this review, we focus on IL-17A and keratinocyte interaction regarding psoriasis pathogenesis.
Highlights
Psoriasis is an immune-mediated chronic skin disease characterized by epidermal hyperproliferation, an intraepidermal accumulation of neutrophils, and dermal inflammatory cell infiltrates that are composed of dendritic cells and T cells [1]
In the promoter region of the IVL gene, there is a binding site for CAAT-enhancer-binding proteins (C/EBP), and the C/EBP transcription factor is necessary for the appropriate and continuous production of IVL protein [176]. These results suggest that interleukin 17A (IL-17A) accelerates keratinocyte differentiation by increasing C/EBPβ protein in keratinocytes [168,169,173]
Keratinocytes produce a variety of antimicrobial peptides and cytochemokines in response to IL-17A
Summary
Psoriasis is an immune-mediated chronic skin disease characterized by epidermal hyperproliferation, an intraepidermal accumulation of neutrophils, and dermal inflammatory cell infiltrates that are composed of dendritic cells and T cells [1]. The skin lesion usually appears on the sites with frequent trauma such as elbows and knees [8,9] This injury-induced development of psoriasis is called Koebner phenomenon [8,9]. The topical application of steroids and vitamin D3 analogues inhibits psoriatic inflammation and normalizes epidermal differentiation [38,39] Systemic treatments, such as methotrexate, cyclosporine, phototherapy, and the phosphodiesterase 4 inhibitor apremilast, are useful for patients with extensive lesions [40,41,42,43,44,45]. Reductions in comorbid cardiovascular events and systemic inflammation have been reported in patients with psoriasis treated with anti-TNF/IL23/IL17 biologics [65,66]. We will focus on the multifaceted biological response in keratinocytes stimulated by IL-17A with regard to psoriatic pathogenesis
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