Guttate psoriasis is associated with an intermediate phenotype of impaired Langerhans cell migration

Eaton, Laura; Chularojanamontri, Leena; Ali, Fahad; Theodorakopoulou, Eleni; Dearman, R.J.; Kimber, Ian; Griffiths, C.E.M.

doi:10.1111/bjd.12960

Cited by 11 publications

(17 citation statements)

References 7 publications

(16 reference statements)

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“…In this context, UV phototherapy diminishes the number of Langerhans cells in the skin that may significantly contribute to its antipsoriatic properties by taking away stimuli such as the production and release of nitric oxide and epidermal growth factor which regulate keratinocyte proliferation . Moreover, impaired Langerhans cell migration in psoriasis was normalized after effective treatment (with TNF inhibitors, ustekinumab or fumaric acid), irrespective of the agent administered . The resetting of the capacity of Langerhans cells to emigrate from the skin to lymph nodes may be a particular component of the therapeutic effect of UV in psoriasis, similar to the result of photohardening in patients with PLE, in whom the migratory capacity of Langerhans cells normalizes after repetitive treatment with suberythemal UVB .…”

Section: How Does Phototherapy Work In Psoriasis?mentioning

confidence: 99%

“…45 Moreover, impaired Langerhans cell migration in psoriasis was normalized after effective treatment (with TNF inhibitors, ustekinumab or fumaric acid), irrespective of the agent administered. 46,47 The resetting of the capacity of Langerhans cells to emigrate from the skin to lymph nodes may be a particular component of the therapeutic effect of UV in psoriasis, similar to the result of photohardening in patients with PLE, in whom the migratory capacity of Langerhans cells normalizes after repetitive treatment with suberythemal UVB. 44,48 Photohardening may affect the complex cytokine milieu in the skin and thereby normalizing cellular migration processes after subsequent UV exposure 49,50 (Table 1)…”

Section: How Does Phototherapy Work In Psoriasis?mentioning

confidence: 99%

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Desired response to phototherapy vs photoaggravation in psoriasis: what makes the difference?

Wolf

Weger

Patra

et al. 2016

Experimental Dermatology

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Psoriasis commonly responds beneficially to UV radiation from natural sunlight or artificial sources. Therapeutic mechanisms include the proapoptotic and immunomodulating effects of UV, affecting many cells and involving a variety of pro-and anti-inflammatory cytokines, downregulating the Th17/IL-23 response with simultaneous induction of regulatory immune cells. However, exposure to UV radiation in a subset of psoriasis patients leads to exacerbation of the disease. We herein shed light on the predisposing factors of photosensitive psoriasis, including genetics (such as HLACw*0602 or CARD14), gender and coexisting photodermatoses such as polymorphic light eruption (PLE) in the context of potential molecular mechanisms behind therapeutic photoresponsiveness or photoaggravation. UV-induced damage/pathogenassociated molecular patterns, damage to self-coding RNA (signalling through Toll-like receptors), certain antimicrobial peptides and/or inflammasome activation may induce innate immunity, leading to psoriasis at the site of UV exposure when there is concomitant, predisposing resistance against UV-induced suppression of the adaptive immune response (like in PLE) that otherwise would act to reduce psoriasis. K E Y W O R D S

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Section: How Does Phototherapy Work In Psoriasis?mentioning

confidence: 99%

Section: How Does Phototherapy Work In Psoriasis?mentioning

confidence: 99%

Desired response to phototherapy vs photoaggravation in psoriasis: what makes the difference?

Wolf

Weger

Patra

et al. 2016

Experimental Dermatology

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“…In addition, the splicing signature comparison workflow 240 was applied to infer the potential candidate SFs that may regulate splicing changes in psoriasis. 37 . Our analysis identified a conserved splicing pattern in Cttn, suggesting the potential 265 contribution of the alternative splicing of Cttn to psoriasis.…”

Section: Confirming the Key Splicing Regulators In Humans 180mentioning

confidence: 99%

“…As another example, the splicing pattern 266 of STE20-like kinase (Slk) was strongly conserved (ΔΨ > 10%) between mice and humans. Since 267 cell migration is inhibited in psoriasis 37 , the splicing changes of Slk may contribute to psoriasis by 268 affecting cell migration 38 . The above results of our conservation analysis demonstrate that splicing 269 changes potentially affect several processes related to psoriasis.…”

Section: Confirming the Key Splicing Regulators In Humans 180mentioning

confidence: 99%

Genome-wide transcriptome analysis identifies alternative splicing regulatory network and key splicing factors in mouse and human psoriasis

2018

Preprint

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Genome-wide transcriptome analysis identifies alternative splicing regulatory network andPsoriasis is a chronic inflammatory disease that affects the skin, nails, and joints. For 23 understanding the mechanism of psoriasis, though, alternative splicing analysis has received 24 relatively little attention in the field. Here, we developed and applied several computational 25 analysis methods to study psoriasis. Using psoriasis mouse and human datasets, our differential 26 alternative splicing analyses detected hundreds of differential alternative splicing changes. Our 27 analysis of conservation revealed many exon-skipping events conserved between mice and 28 humans. In addition, our splicing signature comparison analysis using the psoriasis datasets and 29 our curated splicing factor perturbation RNA-Seq database, SFMetaDB, identified nine candidate 30 splicing factors that may be important in regulating splicing in the psoriasis mouse model dataset. 31Three of the nine splicing factors were confirmed upon analyzing the human data. Our 32 computational methods have generated predictions for the potential role of splicing in psoriasis. 33Future experiments on the novel candidates predicted by our computational analysis are expected 34 to provide a better understanding of the molecular mechanism of psoriasis and to pave the way for 35 new therapeutic treatments. 36

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“…Skin explants have been used to investigate normal growth and differentiation as well as study the effects of pharmacologic agents that modulate skin growth and differentiation in vivo 8. Skin explants have recently been utilized in various areas in dermatologic research, including immunology, microbiology, and dermal sensation9,10,11.…”

Section: Introductionmentioning

confidence: 99%

Usefulness of Skin Explants for Histologic Analysis after Fractional Photothermolysis

et al. 2015

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BackgroundFractional laser resurfacing treatment has been extensively investigated and is widely used. However, the mechanism underlying its effects is poorly understood because of the ethical and cosmetic problems of obtaining skin biopsies required to study the changes after laser treatment.ObjectiveTo evaluate the usefulness of human skin explants for the investigation of fractional photothermolysis.MethodsFull-thickness discarded skin was treated in 4 ways: no treatment (control), fractional carbon dioxide laser, fractional Er:YAG laser, and fractional 1,550-nm erbium-doped fiber laser. Both treated and non-treated skin samples were cultured ex vivo at the air-medium interface for 7 days. Frozen tissue was sectioned and stained with hematoxylin & eosin for histologic examination and nitro blue tetrazolium chloride for viability testing.ResultsSkin explants cultured for up to 3 days exhibited histologic changes similar to those observed in in vivo studies, including microscopic treatment zones surrounded by a thermal coagulation zone, re-epithelialization, and formation of microscopic epidermal necrotic debris. However, the explant structure lost its original form within 7 days of culture. The viability of skin explants was maintained for 3 days of culture but was also lost within 7 days.ConclusionThe skin explant model may be a useful tool for investigating the immediate or early changes following fractional photothermolysis, but further improvements are required to evaluate the long-term and dermal changes.

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Guttate psoriasis is associated with an intermediate phenotype of impaired Langerhans cell migration

Cited by 11 publications

References 7 publications

Desired response to phototherapy vs photoaggravation in psoriasis: what makes the difference?

Desired response to phototherapy vs photoaggravation in psoriasis: what makes the difference?

Genome-wide transcriptome analysis identifies alternative splicing regulatory network and key splicing factors in mouse and human psoriasis

Usefulness of Skin Explants for Histologic Analysis after Fractional Photothermolysis

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