In:
The Journal of Immunology, The American Association of Immunologists, Vol. 190, No. 1_Supplement ( 2013-05-01), p. 59.14-59.14
Abstract:
Atopic dermatitis (AD) is a chronic inflammatory skin disease. Repeated epicutaneous applications of allergen (Dermatophagoides farinae extract) and staphylococcal enterotoxin B induced AD-like skin lesions on mice. We showed that this dermatitis requires mast cells and T cells, but not B cells or eosinophils, for full expression of dermatitis. The clinical severity of dermatitis was correlated with numbers of mast cells. GM-CSF, TSLPR and FcϵRI were required to attain maximal clinical scores. Moreover, high similarity was found in gene expression patterns in allergen-induced lesional skin and human AD skin, supporting the clinical relevance of our mouse model. We have also been studying spontaneously occurring AD-like skin lesions in phospholipase C (PLC)-β3-deficient mice. Mast cells, but not T or B cells, were indispensable for the development of skin lesions. Remarkable abundance of mast cells in the skin of PLC-β3-/- mice was due to the loss of an adaptor function of PLC-β3 to inhibit IL-3-mediated proliferation of mast cells via SHP-1-mediated suppression of Stat5 activity. Consistent with this, increased numbers of mast cells with phosphorylated Stat5 were found in lesional skin of PLC-β3-/- mice. Therefore, this study demonstrates a critical importance of mast cells in AD and suggests that AD development is controlled by elements of the Stat5-activating pathways, as well as other components (PLC-β3 and SHP-1) of the recently discovered multi-molecular complex SPS.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.190.Supp.59.14
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2013
detail.hit.zdb_id:
1475085-5
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