Psoriasis: Keratinocytes or Immune Cells – Which Is the Trigger?

Benhadou, Farida; Mintoff, Dillon; Marmol, Véronique Del

doi:10.1159/000495291

Cited by 178 publications

(147 citation statements)

References 99 publications

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“…[54] Taken together, these preclinical in vivo findings in instructive mouse models suggest a key role for keratinocytes in the orchestration of vascular remodelling and infiltration of immune cells in psoriasis. [55] However, it is now well-appreciated that psoriasis develops as the result of a complex crosstalk between keratinocytes and immune cells. [55] Therefore, it is conceivable that VEGF-A drives the development of psoriasis not only through upregulated angiogenesis, but F I G U R E 2 VEGF signalling pathways.…”

Section: Preclini C Al E Viden Ce For a Role Of Veg F-a In Psoria S Ismentioning

confidence: 99%

Vascular endothelial growth factor‐A as a promising therapeutic target for the management of psoriasis

Luengas‐Martinez

Hardman‐Smart

Paus

et al. 2020

Experimental Dermatology

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Vascular endothelial growth factor‐A (VEGF‐A), the main angiogenic mediator, plays a critical role in the pathogenesis of several inflammatory immune‐mediated diseases, including psoriasis. Even though anti‐angiogenic therapies, such as VEGF inhibitors, are licensed for the treatment of various cancers and eye disease, VEGF‐targeting interventions are not part of current psoriasis therapy. In this viewpoint essay, we argue that the existing preclinical research evidence on the role of VEGF‐A in the pathogenesis of psoriasis as well as clinical observations in patients who have experienced psoriasis remission during oncological anti‐VEGF‐A therapy strongly suggests to systematically explore angiogenesis targeting also in the management of psoriasis. We also point out that some psoriasis therapies decrease circulating levels of VEGF‐A and normalise the psoriasis‐associated vascular pathology in the papillary dermis of plaques of psoriasis and that a subset of patients with constitutionally high levels of VEGF‐A may benefit most from the anti‐angiogenic therapy we advocate here. Given that novel, well‐targeted personalised medicine therapies for the development of psoriasis need to be developed, we explore the hypothesis that VEGF‐A and signalling through its receptors constitute a promising target for therapeutic intervention in the future management of psoriasis.

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Section: Preclini C Al E Viden Ce For a Role Of Veg F-a In Psoria S Ismentioning

confidence: 99%

Vascular endothelial growth factor‐A as a promising therapeutic target for the management of psoriasis

Luengas‐Martinez

Hardman‐Smart

Paus

et al. 2020

Experimental Dermatology

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“…Beyond this, keratinocytes also produce TNF-α, which stimulates the transformation of macrophages into dendritic cells, which are among the main players in the establishment of chronic inflammation [54]. Following in this direction, the effect of cyanobacteria extracts on keratinocyte proliferation was assessed by measuring their effects on cell viability after periods of 24 and 48 h of exposition to the extracts through the MTT assay (Figure 3).…”

Section: Antiproliferative Potentialmentioning

confidence: 99%

Carotenoids from Cyanobacteria: A Biotechnological Approach for the Topical Treatment of Psoriasis

2020

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In this study, five cyanobacteria strains (Alkalinema aff. pantanalense LEGE15481, Cyanobium gracile LEGE12431, Nodosilinea (Leptolyngbya) antarctica LEGE13457, Cuspidothrix issatschenkoi LEGE03282 and Leptolyngbya-like sp. LEGE13412) from the Blue Biotechnology and Ecotoxicology Culture Collection (LEGE CC) of CIIMAR were explored for their biotechnological potential in the treatment of psoriasis. Different extracts were characterized for their pigment profile by HPLC-PDA. The antioxidant potential of the extracts was assessed against the superoxide anion radical (O2•-). Their anti-inflammatory and antiproliferative potential was assessed in vitro using the macrophages RAW 264.7 and the human keratinocytes HaCaT as cell-line models, respectively. Terrestrial and freshwater strains presented the highest carotenoid content (33193−63926 μg/g dry extract), with all-trans-β-carotene, zeaxanthin, echinenone and lutein derivatives being the most abundant carotenoids. Acetone was the most effective solvent for pigment extraction. The acetone extracts presented the lowest IC50 values (0.29−0.38 mg dry extract/mL) regarding O2•- scavenging, and revealed anti-inflammatory potential, with N. antarctica LEGE13457, A. pantanalense LEGE15481 and Leptolyngbya-like sp. LEGE13412 reducing the nitric oxide (NO) in RAW 264.7 cell culture medium in about 25% (p < 0.05). With the exception of A. pantanalense LEGE15481, all the extracts significantly reduced keratinocyte proliferation (p < 0.05), demonstrating a selective toxicity among the different cell lines. Overall, Leptolyngbya-like sp. LEGE13412 and N. antarctica LEGE13457 seem promising for further exploitation in the framework of psoriasis, due to their antioxidant, anti-inflammatory and antiproliferative potential.

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“…The histology of a psoriatic plaque perfectly shows the complexity of the disease: it shows epidermal hyperplasia caused by an abnormal proliferation and differentiation of KCs, dermal inflammatory infiltrates composed of dermal DCs, macrophages, T cells, neutrophils and neovascularization [15,26,85,86]. In psoriatic skin, the transformation from basal KCs to corneocytes occurs in around 5 days, in comparison with the roughly 50-day process in healthy skin [15].…”

Section: The Pathogenesis Of Psoriasismentioning

confidence: 96%

“…In pre-psoriatic skin, injured KCs activated by trigger factors produce AMPs, IL-1 family cytokines and chemokines that act as chemoattractants for infiltrating LCs, pDCs, mDCs, neutrophils, MCs and macrophages [15,85,106]. The attracted pDCs initiate psoriasis inflammation [107] and are activated by the AMP-nucleic-acid complexes.…”

Section: Adamtsl5mentioning

confidence: 99%

“…The synthesis of cells and their continuous movement toward the outer skin layers are responsible for the dynamic character of this important organ. Indeed, the skin turnover relates to the transformation of basal KCs into anucleate corneocytes, over a period of approximately 50 days in healthy skin [15]. The stratum basale contains KCs, melanocytes and Merkel cells, highly specialized cells which have contact with many axon terminals [8].…”

mentioning

confidence: 99%

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The Brain–Skin Connection and the Pathogenesis of Psoriasis: A Review with a Focus on the Serotonergic System

Martins¹,

Ascenso²,

Ribeiro³

et al. 2020

Cells

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Psoriasis is a common non-communicable chronic immune-mediated skin disease, affecting approximately 125 million people in the world. Its pathogenesis results from a combination of genetic and environmental factors. The pathogenesis of psoriasis seems to be driven by the interaction between innate immune cells, adaptive immune cells and keratinocytes, in a process mediated by cytokines (including interleukins (IL)-6, IL-17 and IL-22, interferon and tumor necrosis factor) and other signaling molecules. This leads to an inflammatory process with increased proliferation of epidermal cells, neo-angiogenesis and infiltration of dendritic cells in the skin. Dysfunctional de novo glucocorticoid synthesis in psoriatic keratinocytes and the skin microbiome have also been suggested as mediators in the pathogenesis of this disease. To understand psoriasis, it is essential to comprehend the processes underlying the skin immunity and neuroendocrinology. This review paper focuses on the skin as a neuroendocrine organ and summarizes what is known about the skin immune system, the brain–skin connection and the role played by the serotonergic system in skin. Subsequently, the alterations of neuroimmune processes and of the serotonergic system in psoriatic skin are discussed, as well as, briefly, the genetic basis of psoriasis.

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Psoriasis: Keratinocytes or Immune Cells – Which Is the Trigger?

Cited by 178 publications

References 99 publications

Vascular endothelial growth factor‐A as a promising therapeutic target for the management of psoriasis

Vascular endothelial growth factor‐A as a promising therapeutic target for the management of psoriasis

Carotenoids from Cyanobacteria: A Biotechnological Approach for the Topical Treatment of Psoriasis

The Brain–Skin Connection and the Pathogenesis of Psoriasis: A Review with a Focus on the Serotonergic System

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