PGP 9.5 distribution patterns in biopsies from early lesions of atopic dermatitis

Emtestam, Lennart; Hagströmer, Lena; Dou, Ying-Chun; Sartorius, Karin; Johansson, Ӧlle

doi:10.1007/s00403-012-1246-0

Cited by 17 publications

(11 citation statements)

References 10 publications

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“…Increased cutaneous innervation has been reported in mouse models of Ox-mediated CHS [5] and in human atopic dermatitis [24]. We found 8-10-fold increase in densities of CGRP + (Figure 3A-C, D) and PGP 9.5 + (Figure 3E-G, H) nerve fibers in sensitized mice challenged once with Ox vs. vehicle 48 hours after challenge.…”

Section: Resultssupporting

confidence: 71%

Contact Hypersensitivity to Oxazolone Provokes Vulvar Mechanical Hyperalgesia in Mice

et al. 2013

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The interplay among pain, allergy and dysregulated inflammation promises to yield significant conceptual advances in immunology and chronic pain. Hapten-mediated contact hypersensitivity reactions are used to model skin allergies in rodents but have not been utilized to study associated changes in pain perception in the affected skin. Here we characterized changes in mechanical hyperalgesia in oxazolone-sensitized female mice challenged with single and repeated labiar skin exposure to oxazolone. Female mice were sensitized with topical oxazolone on their flanks and challenged 1-3 times on the labia. We then measured mechanical sensitivity of the vulvar region with an electronic pressure meter and evaluated expression of inflammatory genes, leukocyte influx and levels of innervation in the labiar tissue. Oxazolone-sensitized mice developed vulvar mechanical hyperalgesia after a single labiar oxazolone challenge. Hyperalgesia lasted up to 24 hours along with local influx of neutrophils, upregulation of inflammatory cytokine gene expression, and increased density of cutaneous labiar nerve fibers. Three daily oxazolone challenges produced vulvar mechanical hyperalgesic responses and increases in nerve density that were detectable up to 5 days post-challenge even after overt inflammation resolved. This persistent vulvar hyperalgesia is resonant with vulvodynia, an understudied chronic pain condition that is remarkably prevalent in 18-60 year-old women. An elevated risk for vulvodynia has been associated with a history of environmental allergies. Our pre-clinical model can be readily adapted to regimens of chronic exposures and long-term assessment of vulvar pain with and without concurrent inflammation to improve our understanding of mechanisms underlying subsets of vulvodynia and to develop new therapeutics for this condition.

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Section: Resultssupporting

confidence: 71%

Contact Hypersensitivity to Oxazolone Provokes Vulvar Mechanical Hyperalgesia in Mice

et al. 2013

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“…37 These findings may partly explain the increased epidermal sensory nerve fibre density in AD patients. [38][39][40][41][42] which probably accounts for the higher 'skin sensitivity' in AD patients to minimal stimuli. This is in line with the assumption that neural changes occur in direct response to on-going inflammatory signals in AD.…”

Section: Il-31 In Neuro-immune Communicationmentioning

confidence: 99%

Interleukin-31: The ‘itchy’ cytokine in inflammation and therapy

Datsi¹,

Alam²,

Faried³

et al. 2020

Preprint

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Interleukin-31 has been implicated in the pathophysiology of multiple atopic disorders such as atopic dermatitis (AD), rhinitis and airway hyperreactivity. In AD, IL-31 has been identified as one of the main ‘drivers’ of its cardinal symptom pruritus. Here, we aim to summarize the mechanisms by which IL-31 modulates inflammatory and allergic diseases. TH2 cells play a central role in AD and release high levels of TH2-produced cytokines including IL-31, thereby mediating inflammatory responses, initiating immunoregulatory circuits, and stimulating itch and neuronal outgrowth through activation of the heterodimer receptor IL-31 receptor alpha (IL31RA)/Oncostatin M receptor β. IL31RA expression is found on human and murine dorsal root ganglia neurons, epithelial cells including keratinocytes as well as various innate immune cells. IL-31 is a critical cytokine involved in neuro-immune communication, which opens new avenues for cytokine modulation in neuroinflammatory diseases including AD/pruritus, as validated by recent clinical trials using an anti-IL-31 antibody. Accordingly, inhibition of IL-31 downstream signaling may be a beneficial approach for various inflammatory diseases including prurigo nodularis. For example, whether downstream JAK inhibitors directly block IL-31-mediated-signaling needs to be clarified. Targeting the IL-31/IL31RA/OSMRβ axis appears to be a promising approach for inflammatory, neuroinflammatory and pruritic disorders in the future.

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“…Moreover, a significantly higher percentage of positive samples was obtained from lesional compared to nonlesional skin of dogs with AD. These results parallel the higher density of IENFs found in human AD skin …”

Section: Discussionmentioning

confidence: 99%

“…In contrast, atopic dermatitis (AD) is one of the rare human diseases in which an increase in IENF densities has been described in lesional skin compared to both normal‐looking atopic and healthy human skin . These observations eventually led to studies evaluating new therapeutic approaches to reduce the number of IENFs, either by limiting the effect of nerve elongation factors (NEFs) such as nerve growth factor (NGF) or by increasing the action of nerve repulsion factors (NRFs) such as semaphorin 3A .…”

Section: Introductionmentioning

confidence: 99%