Key Signaling Pathways in Psoriasis: Recent Insights from Antipsoriatic Therapeutics

Abstract

Psoriasis is a common chronic inflammatory skin disease associated with several comorbidities and reduced quality of life. In the past decades, highly effective targeted therapies have led to breakthroughs in the management of psoriasis, providing important insights into the pathogenesis. This article reviews the current concepts of the pathophysiological pathways and the recent progress in antipsoriatic therapeutics, highlighting key targets, signaling pathways and clinical effects in psoriasis.

Climatotherapy at the Dead Sea for psoriasis is a highly effective anti‐inflammatory treatment in the short term: An immunohistochemical study

“…With the approval of newer biologics such as IL-23 and IL-17 inhibitors, complete skin clearance is often attainable. 6,[62][63][64] Secukinumab is an IL-17A inhibitor and its use results in a reduction in LS epidermal thickness to NL baseline levels and a reduction in CD11c + DCs and CD163 + cells after 12 weeks. 65 A reduction of CD3 + T cells and proliferation (Ki67) was also observed after 6 weeks.…”

“…4,5 Several treatment options exist for psoriasis; however, traditional systemic drugs have well-known clinical limitations and potential side effects. 6 Ultraviolet (UV) irradiation with either artificial UVA or UVB light or with natural sunlight is another treatment option. 7 This can be combined with salt water 8,9 or alternatively as a combination with more favourable climate conditions termed climatotherapy.…”

“…Furthermore, the inflammation results in keratinocyte hyperproliferation, dysfunction and production of cytokines, thus sustaining the inflammatory loop 4,5 . Several treatment options exist for psoriasis; however, traditional systemic drugs have well‐known clinical limitations and potential side effects 6 . Ultraviolet (UV) irradiation with either artificial UVA or UVB light or with natural sunlight is another treatment option 7 .…”

Exploring the Links between Obesity and Psoriasis: A Comprehensive Review

“…Psoriatic arthritis is seronegative inflammatory arthritis [ 29 ], in which a critical risk factor for its occurrence is the presence of obesity [ 125 ]. Psoriasis may occur before, simultaneously, or after arthritis has occurred or never appeared; it may be polyarthritis, oligoarthritis, arthritis mutilans or spondylitis [ 126 ]; and it affects a quarter of all cases of psoriasis [ 127 ].…”

Use of Cytokine Mix-, Imiquimod-, and Serum-Induced Monoculture and Lipopolysaccharide- and Interferon Gamma-Treated Co-Culture to Establish In Vitro Psoriasis-like Inflammation Models

“…Immune cells (mainly neutrophils) expressing the CXCL1, CXCL2, and CXCL8 receptors migrate to the skin along a chemokine gradient [ 8 , 9 ]. Key processes during disease persistence are the presentation of putative autoantigens to T lymphocytes and the release of interleukin 23 (IL-23) by skin dendritic cells, the production of proinflammatory mediators, such as IL-17A, IL-17F, and IL-22, by Th17 and Tc17 lymphocytes, and interferon gamma (IFN-γ) and tumour necrosis factor alpha (TNF-α) by Th1 and Tc1 cells [ 10 , 11 ]. These mediators act on keratinocytes, leading to their activation and proliferation as well as the production of antimicrobial peptides (e.g., LL-37 cathelicidin and β-defensins), chemokines (e.g., CXCL9 via CXCL11 and CCL20), and S100 proteins (e.g., S100A7 via S100A9) [ 12 , 13 ].…”