Development of Atopic Dermatitis-Like Skin Lesions in STAT6-Deficient NC/Nga Mice

Yagi, Ryouji; Nagai, Haruko; Iigo, Yutaka; Akimoto, Toshihiko; Arai, Takao; Kubo, Masato

doi:10.4049/jimmunol.168.4.2020

Cited by 121 publications

(108 citation statements)

References 44 publications

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“…1E). Therefore, P6 administration on skin lesions did not affect systemic Ig production, which suggested that the AD-like skin disorder in NC/Nga mice does not depend on the serum IgE, as reported previously (29).…”

Section: P6-nano Treatment Ameliorates Adsupporting

confidence: 83%

Pyridone 6, a Pan-JAK Inhibitor, Ameliorates Allergic Skin Inflammation of NC/Nga Mice via Suppression of Th2 and Enhancement of Th17

Nakagawa

Yoshida

Asakawa

et al. 2011

The Journal of Immunology

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Atopic dermatitis (AD) is a common pruritic inflammatory disease triggered by a defective skin barrier and immunodysregulation. AD has been considered a typical example of a Th2 response associated with allergic disease. In the early phases of the disease, symptoms include IgE hyperproduction, eosinophil accumulation, and mast cell activation; in the chronic phase, a Th1-dominant immune response is also observed at the sites of AD skin lesions. The role of IL-17–producing Th (Th17) cells in AD has not been established. In the current study, we found that pyridone 6 (P6), a pan-JAK inhibitor, delayed the onset and reduced the magnitude of skin disease in an AD-like skin-disease model of NC/Nga mice. P6 reduced IFN-γ and IL-13, whereas it enhanced IL-17 and IL-22 expression. In vitro, P6 also inhibited both Th1 and Th2 development, whereas it promoted Th17 differentiation from naive T cells when present within a certain range of concentrations. This was probably because P6 strongly inhibited STAT1, STAT5, and STAT6 phosphorylation, whereas STAT3 phosphorylation was less efficiently suppressed by P6 at the same concentration. Furthermore, IL-22 protects keratinocytes from apoptosis induced by IFN-γ, and administration of IL-17 and IL-22 partially ameliorated skin diseases in NC/Nga mice. These results suggested that the JAK inhibitor P6 is therapeutic for AD by modulating the balance of Th2 and Th17.

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Section: P6-nano Treatment Ameliorates Adsupporting

confidence: 83%

Pyridone 6, a Pan-JAK Inhibitor, Ameliorates Allergic Skin Inflammation of NC/Nga Mice via Suppression of Th2 and Enhancement of Th17

Nakagawa

Yoshida

Asakawa

et al. 2011

The Journal of Immunology

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“…Peng et al (33) reported that CpG-ODN vaccinations may fail to down-regulate ongoing IgE responses and the application induces a transient skin delayed-type hypersensitivity with production of IFN-␥. Moreover, STAT-6-deficient NC/Nga mice, which fail to produce IgE and Th2 cytokines and highly express IFN-␥ in skin lesions, developed AD-like skin lesions at an equivalent frequency to normal NC/Nga littermates (34). But another report suggested that CpG-ODN could reserve the established eosinophilic inflammation in the skin with IFN-␥ production (32).…”

Section: Discussionmentioning

confidence: 99%

Suppression of Skin Lesions by Transdermal Application of CpG-Oligodeoxynucleotides in NC/Nga Mice, a Model of Human Atopic Dermatitis

Inoue

Aramaki

2007

The Journal of Immunology

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Atopic dermatitis (AD) is a pruritic inflammatory skin disease characterized by an elevation of the total IgE level in plasma, the infiltration of mast cells and eosinophils, and the expression of cytokines by Th2 cells. NC/Nga mice kept in conventional conditions are known to develop skin lesions resembling human AD. We examined in this study the alterations of immune response in NC/Nga mice kept in conventional conditions, following transdermal application of CpG-oligodeoxynucleotides (ODN), which plays a critical role in immunity via the augmentation of Th1-type and suppression of Th2-type responses. CpG-ODN remarkably changed the immune response from type Th2 to Th1 as determined from cytokine mRNA and Ab levels. The serum IgE level was decreased and the expression of IgG2a was up-regulated. The application of CpG-ODN to the skin also decreased inflammatory infiltration of mast cells, and suppression in the skin lesions was observed. Furthermore, the generation of regulatory T cells, which are considered immune suppressive T cells, was observed in the skin on treatment with CpG-ODN. These results suggested CpG-ODN is effective for immunotherapy in patients with AD, which is characterized by Th2-dominated inflammation.

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“…Under conventional conditions, eczematous skin lesions develop at the age of 8 weeks with maximum activity at around 17 weeks and characterized by edema, hemorrhage, erosion, and dryness. The skin lesions are typically localized to the face, ears, neck, and back (Matsuda et al, 1997;Suto et al, 1999;Matsumoto et al, 1999;Yagi et al, 2002). In addition, the elevation of plasma IgE levels correlates with the appearance of the AD-like skin lesions.…”

Section: Introductionmentioning

confidence: 99%

Psychological Stress can Trigger Atopic Dermatitis in NC/Nga Mice: An Inhibitory Effect of Corticotropin-Releasing Factor

Amano

Negishi

Akiyama

et al. 2007

Neuropsychopharmacol

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Atopic dermatitis (AD) is one of the most common inflammatory diseases of the skin and is usually associated with a family history of atopic diathesis. It has been well established that many environmental or psychological factors aggravate AD. However, it is not clear whether psychological stress by itself can trigger AD. We examined the effect of psychological stress on the onset of AD, using an animal model, the NC/Nga mouse. The animals were exposed to the water avoidance stress (WAS) test to induce psychological stress. Additionally, we examined how corticotropin-releasing factor (CRF) affected the development of AD induced by psychological stress. Under specific pathogen-free (SPF) conditions, NC/Nga mice did not develop AD-like skin lesions. In contrast, NC/Nga mice exposed to psychological stress developed AD-like skin lesions along with elevated levels of serum immunoglobulin E even when kept under SPF conditions. The AD-like skin lesions induced by WAS were completely blocked by pretreating the animals with CRF. Our data indicate that a psychological factor is capable of eliciting AD-like skin lesions in NC/Nga mice. It is possible that the inhibitory effect of CRF may be mediated by the functional modification of various cells that have CRF receptors.

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Development of Atopic Dermatitis-Like Skin Lesions in STAT6-Deficient NC/Nga Mice

Cited by 121 publications

References 44 publications

Pyridone 6, a Pan-JAK Inhibitor, Ameliorates Allergic Skin Inflammation of NC/Nga Mice via Suppression of Th2 and Enhancement of Th17

Pyridone 6, a Pan-JAK Inhibitor, Ameliorates Allergic Skin Inflammation of NC/Nga Mice via Suppression of Th2 and Enhancement of Th17

Suppression of Skin Lesions by Transdermal Application of CpG-Oligodeoxynucleotides in NC/Nga Mice, a Model of Human Atopic Dermatitis

Psychological Stress can Trigger Atopic Dermatitis in NC/Nga Mice: An Inhibitory Effect of Corticotropin-Releasing Factor

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