Scanning the Immunopathogenesis of Psoriasis

Abstract

Psoriasis is a chronic inflammatory skin disease, the immunologic model of which has been profoundly revised following recent advances in the understanding of its pathophysiology. In the current model, a crosstalk between keratinocytes, neutrophils, mast cells, T cells, and dendritic cells is thought to create inflammatory and pro-proliferative circuits mediated by chemokines and cytokines. Various triggers, including recently identified autoantigens, Toll-like receptor agonists, chemerin, and thymic stromal lymphopoietin may activate the pathogenic cascade resulting in enhanced production of pro-inflammatory and proliferation-inducing mediators such as interleukin (IL)-17, tumor necrosis factor (TNF)-α, IL-23, IL-22, interferon (IFN)-α, and IFN-γ by immune cells. Among these key cytokines lie therapeutic targets for currently approved antipsoriatic therapies. This review aims to provide a comprehensive overview on the immune-mediated mechanisms characterizing the current pathogenic model of psoriasis.

Switching from Secukinumab to Ustekinumab in Psoriasis Patients: Results from a Multicenter Experience

“…Indeed, IL-23 plays a crucial role in sustaining and amplifying the development of IL-17-producing cells, but also in regulating the expansion of anti-inflammatory T-regulatory cells inducing the expression of other downstream pathogenic cytokines, such as IL-22, IL-17F, and IL-21 [25-28]. Hence, a broader immune modulation and the simultaneous inhibition of multiple pathways induced by ustekinumab might achieve a superior clinical response compared to the selective IL-17A blockade that, in nonresponder patients, because of the development of alternative inflammatory circuits independent of IL-17A signaling, are usually considered of minor pathogenic and therapeutic relevance [1, 29]. Although IL-17A is a key effector cytokine in the IL-23 pathway, the ineffectiveness of IL-17A neutralization does not imply failure of other therapeutics blocking the IL-23/IL-17A axis upstream or downstream.…”

“…Psoriasis is a chronic inflammatory skin disease pathogenically characterized by a marked enhancement of the interleukin (IL)-23/IL-17-mediated signaling [1]. The better understanding of psoriasis pathogenesis, in particular the identification of key immunological pathways contributing to the development of the psoriasis phenotype, led to the development of targeted therapies highly effective in treating psoriasis.…”

TRPV1 mediates inflammation and hyperplasia in imiquimod (IMQ)-induced psoriasiform dermatitis (PsD) in mice

“…Psoriasis is a chronic cutaneous inflammatory condition, which is mediated by dermal leukocytes, including dendritic cells (DCs), T cells, mast cells and neutrophils [1]. T cell activation is thought to be initiated and driven by DCs which produce various proinflammatory cytokines, including IL-6 and IL-23, further driving Th17 cell-mediated inflammation [2].…”

Exosomes in chronic inflammatory skin diseases and skin tumors

“…CD1a is constitutively expressed by LCs of the epidermis . Previous studies have revealed that mast cells are enriched in psoriatic lesions . Multiple lines of evidence support the notion that T cells play a crucial role in the pathogenesis of psoriasis.…”