Development of Numerous Nerve Fibers in the Epidermis of Hairless Mice With Atopic Dermatitis-Like Pruritic Skin Inflammation

Fujii, Masanori; Akita, Keisuke; Mizutani, Nobuaki; Nabe, Takeshi; Kohno, Shigekatsu

doi:10.1254/jphs.fp0070436

Cited by 10 publications

(5 citation statements)

References 29 publications

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“…Sensitization of itch-signaling pathways has been proposed as a critical mechanism underlying chronic itch (41,42). In ACD and atopic dermatitis, nerve fiber densities are increased in the epidermis (43,44). Extension of these nerve fibers into the epidermis may contribute to spontaneous itch, aggravating itch responses and sensitization of itch signaling pathways (42).…”

Section: Discussionmentioning

confidence: 99%

IL-33/ST2 signaling excites sensory neurons and mediates itch response in a mouse model of poison ivy contact allergy

Liu

Tai

Achanta

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

213

195

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Poison ivy-induced allergic contact dermatitis (ACD) is the most common environmental allergic condition in the United States. Case numbers of poison ivy ACD are increasing due to growing biomass and geographical expansion of poison ivy and increasing content of the allergen, urushiol, likely attributable to rising atmospheric CO 2 . Severe and treatment-resistant itch is the major complaint of affected patients. However, because of limited clinical data and poorly characterized models, the pruritic mechanisms in poison ivy ACD remain unknown. Here, we aim to identify the mechanisms of itch in a mouse model of poison ivy ACD by transcriptomics, neuronal imaging, and behavioral analysis. Using transcriptome microarray analysis, we identified IL-33 as a key cytokine up-regulated in the inflamed skin of urushiol-challenged mice. We further found that the IL-33 receptor, ST2, is expressed in small to medium-sized dorsal root ganglion (DRG) neurons, including neurons that innervate the skin. IL-33 induces Ca 2+ influx into a subset of DRG neurons through neuronal ST2. Neutralizing antibodies against IL-33 or ST2 reduced scratching behavior and skin inflammation in urushiol-challenged mice. Injection of IL-33 into urushiol-challenged skin rapidly exacerbated itch-related scratching via ST2, in a histamine-independent manner. Targeted silencing of neuronal ST2 expression by intrathecal ST2 siRNA delivery significantly attenuated pruritic responses caused by urushiol-induced ACD. These results indicate that IL-33/ST2 signaling is functionally present in primary sensory neurons and contributes to pruritus in poison ivy ACD. Blocking IL-33/ST2 signaling may represent a therapeutic approach to ameliorate itch and skin inflammation related to poison ivy ACD.A llergic contact dermatitis (ACD) is a common allergic skin condition caused by environmental or occupational allergens (1). In the United States, the most common cause of ACD is contact with poison ivy, which affects >10 million Americans per year (2, 3). Poison ivy ACD is also a serious occupational hazard, particularly among firefighters, forestry workers, and farmers, accounting for 10% of total U.S. Forest Services losttime injuries, and it often torments outdoor enthusiasts as well (3, 4). The major allergen in poison ivy is urushiol, contained in the oleoresinous sap of the plant and of related plants (e.g., poison oak and poison sumac) (5). An estimated 50-75% of Americans are sensitized to urushiol (6). Elevated atmospheric carbon dioxide and warming temperatures have increased the biomass of poison ivy and related plants, widened their geographic distribution, and increased plant urushiol content (7). These factors will likely increase allergenicity and result in even larger case numbers of poison ivy ACD in the future (8).The clinical manifestations of poison ivy-induced ACD are intense and persistent itch (pruritus), burning sensation, skin rashes, and swelling, followed by the appearance of vesicles in severe cases (2, 3, 9). Skin inflammation and pruritus ...

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Section: Discussionmentioning

confidence: 99%

IL-33/ST2 signaling excites sensory neurons and mediates itch response in a mouse model of poison ivy contact allergy

Liu

Tai

Achanta

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

213

195

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“…Previous studies have demonstrated that nerve fibres were increased in the skin of atopic dermatitis or atopic‐dermatitis‐like pruritic skin inflammation . Thus, inhibition of nerve fibre penetration could be an appropriate strategy for treating skin diseases characterized by pruritus.…”

Section: Discussionmentioning

confidence: 99%

In vitro formation of organized structure between keratinocytes and dorsal‐root‐ganglion cells

Tsutsumi

Nakatani

Kumamoto

et al. 2012

Experimental Dermatology

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We recently found that the morphology in a co‐culture system of keratinocytes and dorsal‐root ganglion‐derived cells depended on the timing of seeding of the two cell types. In skin, epidermis is formed first, followed by construction of peripheral nerve structure. Therefore, we hypothesized that formation of peripheral nerve structure in the epidermis might be driven by interaction between keratinocytes and nerve cells. In the present study, we tested this idea by incubating keratinocytes and dorsal‐root ganglion cells in a spatially separated manner and observing the morphological changes in the co‐culture system. Extension of nerve fibre‐like structures from the ganglion cells was observed, and within 3 days after seeding, many nerve fibre‐like extensions penetrated into the keratinocyte cluster, subsequently forming a network that appeared to resemble the cutaneous peripheral nervous system. Our present model may be useful for studying the formation of peripheral nerve structure in the skin.

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“…In HR-AD diet-fed HR-1 mice, nerve fibers markedly increased in the epidermis (24). The increase in intraepidermal nerve fibers, as well as the skin barrier dysfunction, plays a crucial role in the increased scratching behavior.…”

Section: Effects Of Wasabi Rhizome Extract On Scratching Behaviormentioning

confidence: 97%

The Effect of Wasabi Rhizome Extract on Atopic Dermatitis-Like Symptoms in HR-1 Hairless Mice

Nagai¹,

Okunishi²

2009

J Nutr Sci Vitaminol

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SummaryWe investigated the effect of wasabi rhizome extract on atopic dermatitis (AD) model mice. The wasabi extract was fed to the HR-1 hairless mice, which develop AD-like symptoms with a special diet (HR-AD diet). The extract was expected to reduce the symptoms induced. Wasabi rhizome-containing HR-AD diet (5% and 10%) reduced the scratching behavior, and the 10% wasabi rhizome HR-AD diet significantly reduced scratching behavior on days 28, 35 and 42. Plasma components (histamine, eotaxin, IgE and thymus and activation-regulated chemokine (TARC)) were decreased in the 10% wasabi rhizome HR-AD diet. In histopathological examinations (toluidine blue (T.B.), major basic protein (MBP), CD4, IL-4, IL-5, eotaxin, TARC and IgE), the wasabi rhizome-containing HR-AD diet (5% and 10%) significantly reduced the number of positive stained cells. These results suggested that the wasabi rhizome extract improved the AD-like symptoms of HR-1 hairless mice.

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Development of Numerous Nerve Fibers in the Epidermis of Hairless Mice With Atopic Dermatitis-Like Pruritic Skin Inflammation

Cited by 10 publications

References 29 publications

IL-33/ST2 signaling excites sensory neurons and mediates itch response in a mouse model of poison ivy contact allergy

IL-33/ST2 signaling excites sensory neurons and mediates itch response in a mouse model of poison ivy contact allergy

In vitro formation of organized structure between keratinocytes and dorsal‐root‐ganglion cells

The Effect of Wasabi Rhizome Extract on Atopic Dermatitis-Like Symptoms in HR-1 Hairless Mice

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