TY - JOUR
T1 - Mast cells are required for full expression of allergen/SEB-Induced skin inflammation
AU - Ando, Tomoaki
AU - Matsumoto, Kenji
AU - Namiranian, Siavash
AU - Yamashita, Hirotaka
AU - Glatthorn, Haley
AU - Kimura, Miho
AU - Dolan, Brandon R.
AU - Lee, James J.
AU - Galli, Stephen J.
AU - Kawakami, Yuko
AU - Jamora, Colin
AU - Kawakami, Toshiaki
N1 - Funding Information:
We thank Drs Glenn Dranoff and Steven Ziegler for providing mice and Dr Michael R Comeau (Amgen) for providing anti-TSLP antibody. This study was funded in part by the Atopic Dermatitis Research Network (contract number HHSN26620040033C) supported by the National Institute of Allergy and Infectious Diseases/National Institutes of Health (to TK) and the National Institute of Biomedical Innovation (to KM). HY was supported by a fellowship from Banyu Life Science Foundation International. This study is publication no. 1527 from the La Jolla Institute for Allergy and Immunology.
PY - 2013/12
Y1 - 2013/12
N2 - Atopic dermatitis (AD) is a chronic pruritic inflammatory skin disease. We recently described an animal model in which repeated epicutaneous applications of a house dust mite extract and Staphylococcal enterotoxin B induced eczematous skin lesions. In this study we showed that global gene expression patterns are very similar between human AD skin and allergen/staphylococcal enterotoxin B-induced mouse skin lesions, particularly in the expression of genes related to epidermal growth/differentiation, skin barrier, lipid/energy metabolism, immune response, or extracellular matrix. In this model, mast cells and T cells, but not B cells or eosinophils, were shown to be required for the full expression of dermatitis, as revealed by reduced skin inflammation and reduced serum IgE levels in mice lacking mast cells or T cells (TCRβ -/- or Rag1 -/-). The clinical severity of dermatitis correlated with the numbers of mast cells, but not eosinophils. Consistent with the idea that T helper type 2 (Th2) cells play a predominant role in allergic diseases, the receptor for the Th2-promoting cytokine thymic stromal lymphopoietin and the high-affinity IgE receptor, FcεRI, were required to attain maximal clinical scores. Therefore, this clinically relevant model provides mechanistic insights into the pathogenic mechanism of human AD.
AB - Atopic dermatitis (AD) is a chronic pruritic inflammatory skin disease. We recently described an animal model in which repeated epicutaneous applications of a house dust mite extract and Staphylococcal enterotoxin B induced eczematous skin lesions. In this study we showed that global gene expression patterns are very similar between human AD skin and allergen/staphylococcal enterotoxin B-induced mouse skin lesions, particularly in the expression of genes related to epidermal growth/differentiation, skin barrier, lipid/energy metabolism, immune response, or extracellular matrix. In this model, mast cells and T cells, but not B cells or eosinophils, were shown to be required for the full expression of dermatitis, as revealed by reduced skin inflammation and reduced serum IgE levels in mice lacking mast cells or T cells (TCRβ -/- or Rag1 -/-). The clinical severity of dermatitis correlated with the numbers of mast cells, but not eosinophils. Consistent with the idea that T helper type 2 (Th2) cells play a predominant role in allergic diseases, the receptor for the Th2-promoting cytokine thymic stromal lymphopoietin and the high-affinity IgE receptor, FcεRI, were required to attain maximal clinical scores. Therefore, this clinically relevant model provides mechanistic insights into the pathogenic mechanism of human AD.
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U2 - 10.1038/jid.2013.250
DO - 10.1038/jid.2013.250
M3 - Article
C2 - 23752044
AN - SCOPUS:84887822093
SN - 0022-202X
VL - 133
SP - 2695
EP - 2705
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 12
ER -