Models in the Research Process of Psoriasis

Bocheńska, Katarzyna; Smolińska, Elwira; Moskot, Marta; Jakóbkiewicz‐Banecka, Joanna; Gabig-Cimińska, Magdalena

doi:10.3390/ijms18122514

Cited by 108 publications

(83 citation statements)

References 93 publications

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“…As expected, dilator-implanted mice with H 2 O treatment displayed significant epidermal hyperproliferation, impaired skin barrier function, and release of psoriasis-associated cytokines, in agreement with the findings of our in vitro experiments. IMQ (a TLR7 agonist) and IL-23, which induce psoriasis-like dermatitis, are two agents that are directly used to generate mouse models for studying psoriasis (Boche nska et al, 2017). The role of mechanical stretch in psoriasis pathogenesis is further supported by our observation that inflammation increased markedly in dilator-implanted mice after IMQ or IL-23 treatment.…”

Section: Discussionmentioning

confidence: 89%

Mechanical Stretch Exacerbates Psoriasis by Stimulating Keratinocyte Proliferation and Cytokine Production

Qiao

et al. 2019

Journal of Investigative Dermatology

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Psoriasis is a chronic inflammatory autoimmune skin disease that often occurs in rubbed areas undergoing a strong mechanical stretch, such as the elbows and knees. However, the pathologic role of mechanical tension in psoriasis remains unclear. In this study, we investigated the contribution of keratinocyte mechanical stretch to the clinical features of psoriasis. We found that keratinocyte proliferation and skin barrier-associated gene expression increased significantly after 24 hours of continuous stretching. Additionally, continuous stretching induced the production of psoriasis-associated proinflammatory cytokines, antibacterial peptides, and chemokines in primary human keratinocytes. Furthermore, we established a murine model of skin expansion by implanting a dilator into the dorsum of BALB/c mice to assess the effect of mechanical stretch on the epidermis in vivo. The dilator-implanted mice displayed prominent epidermal hyperproliferation, impaired skin barrier function, and up-regulation of psoriasis-associated cytokines in epidermal keratinocytes. Most importantly, the dilator-implanted psoriatic mice treated with imiquimod or IL-23 displayed an aggravated psoriatic phenotype compared with mice without dilator implantation. Collectively, our results suggest that mechanical stretch can exacerbate psoriatic lesions by promoting cell proliferation and amplifying the production of proinflammatory cytokines by keratinocytes. Thus, our findings provide new insights into the pathogenesis of psoriasis.

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Section: Discussionmentioning

confidence: 89%

Mechanical Stretch Exacerbates Psoriasis by Stimulating Keratinocyte Proliferation and Cytokine Production

Qiao

et al. 2019

Journal of Investigative Dermatology

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“…1). However, as discussed previously, none of the current models is perfectly representing human psoriasis (Bocheńska et al, 2017;Chuang et al, 2018;Hawkes et al, 2018;Swindell et al, 2011). In steady state, direct and indirect sensing (via nociceptive sensory fibers; Cohen et al, 2019;Kashem et al, 2015;Riol-Blanco et al, 2014) of skin microbiota induce dermal DCs to produce basal levels of IL-23, which activates IL-17A and IL-17F secretion of tissue-resident lymphocytes.…”

Section: Dysregulation Of Il-17mentioning

confidence: 83%

Interleukin-17 cytokines: Effectors and targets in psoriasis—A breakthrough in understanding and treatment

Prinz

Sandrock

Mrowietz³

2019

Journal of Experimental Medicine

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The IL-17 cytokine family comprising IL-17A to IL-17F and receptor subunits IL-17RA to IL-17RE represents a genetically ancient intercellular network regulating local tissue homeostasis. Its pivotal role in antifungal defense and its central position in the pathogenesis of inflammatory diseases including psoriasis were discovered only relatively late in the early 2000s. Since the connection of dysregulated IL-17 and psoriasis pathogenesis turned out to be particularly evident, a number of monoclonal antibodies targeting IL-17 pathways have been approved and are used as first line treatment of moderate-to-severe plaque psoriasis and psoriatic arthritis, and further agents are currently in clinical development.

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“…27 Preclinically, there are several mouse models that recapitulate the pathophysiological features of psoriasis, most notably the imiquimod and IL-23 tissue injection models. 30 The latter is a particularly useful model to study the mechanistic undertones of the IL-23/IL-17 pathway in skin inflammation; however, one drawback is that it necessitates repeated (often daily) injections of IL-23 resulting in local tissue trauma, a potential confounding factor to data interpretation. In the current study, an alternative approach was taken by hydrodynamically administrating IL-23 MC DNA into the mouse tail vein.…”

Section: Discussionmentioning

confidence: 99%

Characterization of psoriasiform dermatitis induced by systemic injection of interleukin‐23 minicircles in mice

Leys

Wang

Paulsboe

et al. 2019

The Journal of Dermatology

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The interleukin (IL)‐23/IL‐17 axis plays a central role in the pathogenesis of psoriasis and is elevated in lesional psoriatic skin. Different murine models have been developed to mimic this pathophysiology each carrying specific merits and limitations. In an attempt to address some of these limitations, B10.RIII mice received a single hydrodynamic injection of IL‐23 minicircles (MC) to induce hepatic transcription and the endogenous production of IL‐23. Plasma and ear IL‐23 levels were dose‐dependently (0.3–3 μg) increased in MC injected mice and were sustained over the 14‐day study duration. Beginning on day 7 post‐injection, mice developed dose‐related ear inflammation, histologically confirmed increases in epidermal and dermal area, as well as enhanced neutrophil and macrophage content. Flow cytometry demonstrated increased levels of granulocytes, T cells and monocytes/macrophages in the ear skin, with T cells identified as the main cellular source of IL‐17A. Evaluation of mRNA and protein showed time‐dependent, increased levels of the IL‐23/IL‐17 pathway and inflammatory/microbial cytokines/chemokines in the ear which differed kinetically from circulating levels. An anti‐IL‐23p40 antibody was assessed following both prophylactic administration and administration once the disease was established. Prophylactic dosing completely prevented the development of the ear phenotype across endpoints. Treatment administration showed a dose‐related response, with a maximum inhibition of 64–94%, depending on endpoint. These data demonstrate that the IL‐23 MC model is a useful approach to study IL‐23/IL‐17‐driven skin inflammation and may facilitate preclinical assessment of novel therapies.

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Models in the Research Process of Psoriasis

Cited by 108 publications

References 93 publications

Mechanical Stretch Exacerbates Psoriasis by Stimulating Keratinocyte Proliferation and Cytokine Production

Mechanical Stretch Exacerbates Psoriasis by Stimulating Keratinocyte Proliferation and Cytokine Production

Interleukin-17 cytokines: Effectors and targets in psoriasis—A breakthrough in understanding and treatment

Characterization of psoriasiform dermatitis induced by systemic injection of interleukin‐23 minicircles in mice

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