Allergy Asthma Respir Dis.  2019 Jul;7(3):150-157. 10.4168/aard.2019.7.3.150.

Development of Aspergillus fumigatus-induced chronic atopic dermatitis mouse model

Affiliations
  • 1Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea.
  • 2Department of Pediatrics, Asan Medical Center, Seoul, Korea. jinhoyu@amc.seoul.kr

Abstract

PURPOSE
Atopic dermatitis (AD) is the most common chronic and relapsing inflammatory skin disease with skin barrier defects and altered immune responses. Chronic inflammation leads to irreversible fibrosis in the skin and there is no treatment to completely abolish the inflammation and fibrosis. To prevent or treat the chronic process of AD, it is necessary to develop a murine model of AD that reflects the chronic process to identify the mechanism. The aims of this study were to develop a chronic AD model with a crude extract Aspergillus fumigatus (Af) antigen.
METHODS
We applied Af extract (40 µg) epicutaneously to the dorsal skin of BALB/c mice for 5 consecutive days per week during a period of 5 weeks for a chronic AD model, and 5 consecutive days repeatedly with 2 weeks interval for an acute AD model.
RESULTS
The clinical score and transepidermal water loss were more increased in the chronic AD model than in the acute AD model. Histologic findings showed that more increased epidermal thickness, neutrophil infiltration and hyperkeratosis in the chronic model than in the acute model. Skin fibrosis was more prominent in the chronic model than in the acute model. The mRNA expression levels of transforming growth factor (TGF)-β, thymic stromal lymphopoietin, and interleukin-33 were increased in the skin of the chronic model compared to the acute model. The levels of total IgE, Af-specific IgE, IgG1, and IgG2a were significantly increased in the chronic model compared to controls.
CONCLUSION
The Af-induced chronic AD model showed prominent fibrosis and increased TGF-β expression in the skin, which suggests that these models may be useful in the research for the mechanism of the chronic process in AD.

Keyword

Atopic dermatitis; Mouse; Aspergillus fumigatus

MeSH Terms

Animals
Aspergillus fumigatus
Aspergillus*
Dermatitis, Atopic*
Fibrosis
Immunoglobulin E
Immunoglobulin G
Inflammation
Interleukin-33
Mice*
Neutrophil Infiltration
RNA, Messenger
Skin
Skin Diseases
Transforming Growth Factors
Water
Immunoglobulin E
Immunoglobulin G
Interleukin-33
RNA, Messenger
Transforming Growth Factors
Water

Figure

  • Fig. 1 Models of Aspergillus fumigatus (Af)-induced atopic dermatitis (AD). (A) Schematic protocol of this study. Af extract (40 µg) was epicutaneously applied to the dorsal skin of mice for 5 consecutive days repeatedly with a 2-week interval (acute model) and 5 consecutive days per each week during 5 weeks (chronic model). (B) Macroscopic cutaneous manifestations in the control and Af-induced AD groups. Skin lesions such as erythema, erosions, crusts, and scale were more severe in the chronic mouse model than in the control and acute mouse model. (C, D) Clinical symptom scores and transepidermal water loss in acute and chronic model of Af-induced atopic dermatitis. Clinical symptom scores and transepidermal water loss were increased over time in chronic and acute mouse model. Clinical symptom scores and transepidermal water loss were significantly increased at day 33 in chronic model, compared to those at day 24 in acute mouse model. **P<0.01. ***P<0.001.

  • Fig. 2 Histopathological features of Aspergillus fumigatus (Af)-induced atopic dermatitis models. (A) Skin lesions were stained with hematoxylin & eosin (H&E) to identify eosinophils, neutrophils, and lymphocytes and toluidine blue to identify mast cells (original magnification, ×400; scale bars: left panel=100 µm, right panel=20 µm). (B) Thickening of the epidermal, dermal and hyperkeratosis layers from acute and chronic mouse model showed increased compared to the control mouse model. (C) Numbers of eosinophils, neutrophils, mast cells and lymphocytes were counted under a microscope at ×200 magnification. Data are expressed as mean±standard error of the mean (n=6 per group). *P<0.05. **P<0.01.

  • Fig. 3 Fibrosis features of Aspergillus fumigatus (Af)-induced atopic dermatitis models. (A) Skin collagen deposition from acute and chronic mouse model showed increased compared to control mouse model by Masson's Trichrome staining (original magnification, ×400; scale bars: 100 µm). (B) Fibrosis score from acute and chronic mouse model was significantly increased compared to the control mouse model and that of chronic mouse model was significantly increased compared to the acute mouse model. (C) Collagen content was increased in chronic mouse model compared to the control and acute mouse model. Data are expressed as mean±standard error of the mean (n=6 per group). *P<0.05. **P<0.01.

  • Fig. 4 mRNA expression of transforming growth factor (TGF)-β, interleukin (IL)-13, IL-17A, thymic stromal lymphopoietin (TSLP), IL-25, IL-33, interferon (IFN)-γ, filaggrin in the skin of acute and chronic atopic dermatitis mouse models. The expression of TGF-β, TSLP, and IL-33 mRNA in chronic mouse model was increased compared to acute mouse model. Data are expressed as mean±standard error of the mean (n=6 per group). *P<0.05. **P<0.01.

  • Fig. 5 Serum total IgE, and Af-specific IgE, IgG2a, and IgG1 levels in acute and chronic allergic dermatitis (AD) mouse models. Serum total IgE, and Af-specific IgE levels of both AD models were higher than control mouse model. Af-specific IgG2a and IgG1 levels in chronic mouse model were significantly increased compared to the control and acute mouse model. Data are expressed as mean±standard error of the mean (n=6 per group). **P<0.01. ***P<0.001.


Cited by  1 articles

Atopic dermatitis mouse models
Hyunjung Kim
Allergy Asthma Respir Dis. 2019;7(3):113-115.    doi: 10.4168/aard.2019.7.3.113.


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