Pathophysiology of psoriasis: A review

Abstract

Psoriasis is a complex chronic inflammatory skin disease caused by the dynamic interplay between multiple genetic risk foci, environmental risk factors, and excessive immunological abnormalities. Psoriasis affects approximately 2% of the population worldwide, and dramatic advances have been achieved in the understanding and treatment options for psoriasis. Recent progress in biological therapies has revealed the fundamental roles of tumor necrosis factor‐α, interleukin (IL)‐23p19, and the IL‐17A axis together with skin‐resident immune cells and major signal transduction pathways in the pathogenesis of psoriasis. In addition to IL‐17‐producing T helper17 cells, innate lymphoid cell (ILC)3 induces psoriasis rashes directly without T‐cell/antigen interaction in response to the released antimicrobial peptides from activated keratinocytes and inflammatory cytokines. ILC3 typically expresses retinoic acid receptor‐related orphan receptor gamma t in the nucleus, matures in the presence of IL‐7 and IL‐23, and produces IL‐17 and IL‐22. The number of ILC3s is increased in the blood, psoriasis rash, and even in nonrash areas of psoriatic skin. Psoriasis is significantly associated with cardiovascular disease, metabolic syndrome, and inflammatory disorders, particularly the severe type. The similarity of enterobacteria in the psoriasis gut to that in diabetic patients may be related to its pathogenesis. In the current review, we focus on the pathophysiology of psoriasis in the accelerated immunological inflammatory loop, danger signal from keratinocytes, and cytokines, particularly IL‐17 and IL‐23p19. In addition, pathophysiological speculation with regard to morphology has been supplemented. Finally, the differences and similarities between psoriasis and atopic dermatitis are discussed.

TWEAK functions with TNF and IL-17 on keratinocytes and is a potential target for psoriasis therapy

“…Therefore, it may drive an amplifying loop from IL-23 to IL-17 to IL-36γ and back again to IL-23, thus maintaining the diseased state. All of these cytokines are elevated in psoriasis skin lesions, and correspondingly neutralizing TNF, IL-23 p19, or IL-17A has shown strong therapeutic benefit in patients with psoriasis ( 2 , 8 , 9 ). Although these current treatments have proven efficacy, some patients fail to respond, they become resistant to therapy over time, or their disease comes back when treatment is stopped.…”

Psoriasis and Myasthenia Gravis: A Common Th-17 Pathway

“…These cytokines promote the differentiation of naïve T cells into Th1, Th22, and Th17 cells [3]. IL-17, mainly secreted by Th17 cells, causes abnormal proliferation of keratinocytes and stimulates them to release various chemokines [9], thereby resulting in the formation of classic psoriatic plaques. However, recent articles suggest a role of Th17 cells in anti-ACR-positive myasthenia gravis [5], The suggested mechanism of thymic inflammation involves dysregulation of interferon type I pathway which leads to overexpression of IL-23 and thus to overproduction of IL-17 [10].…”

Notch1/Hes1‑PTEN/AKT/IL‑17A feedback loop regulates Th17 cell differentiation in mouse psoriasis‑like skin inflammation

“…Psoriasis is an immune-mediated chronic inflammatory skin disease, in which intralesional T lymphocytes and their proinflammatory signals trigger keratinocytes to rapidly proliferate and initiate the inflammatory process ( 1 ). Previous studies reported that the IL-23/T helper (Th)17 axis played a crucial role in the pathogenesis of psoriasis ( 2 , 3 ).…”