Mast cells regulate IFN-gamma expression in the skin and circulating IgE levels in allergen-induced skin inflammation.
BACKGROUND
Mast cells are important effector cells in IgE-mediated allergic reactions. They are present in normal skin and increased in skin lesions of patients with atopic dermatitis (AD).


OBJECTIVE
We used mice deficient in mast cells (W/W(v)) to assess the role of these cells in a murine model of allergen-induced skin inflammation induced by repeated epicutaneous sensitization with ovalbumin (OVA); the model exhibits many of the characteristics of AD.


METHODS
Mice deficient in mast cells were sensitized with OVA. Histologic and immunohistochemical examinations, as well as measurements of IL-4 and IFN-gamma mRNA, were performed on OVA-sensitized skin. Total and antigen-specific serum IgE levels were determined.


RESULTS
Infiltration in W/W(v) mice by mononuclear cells, T cells, and eosinophils in OVA-sensitized skin was comparable to that in wild-type (WT) controls. Expression of IL-4 mRNA in sensitized skin sites was similarly increased in WT and W/W(v) mice. However, IFN-gamma mRNA expression was significantly increased in sensitized skin of W/W(v) mice but not in that of WT controls. IL-4 mRNA was readily detectable in unsensitized skin of WT controls but not in that of W/W,(v) mice, whereas expression of IL-12 p40 mRNA was significantly increased in unsensitized skin of W/W(v) mice in comparison with WT controls. Total serum IgE levels were significantly increased after epicutaneous sensitization in W/W(v) mice in comparison with WT controls.


CONCLUSIONS
These results suggest that mast cells regulate IFN-gamma expression in the skin and IgE levels in the circulation in a model of allergen-induced skin inflammation with similarities to AD. This is important, given the role of IFN-gamma in keratinocyte injury in AD and the role of IgE-mediated reactions in exacerbating AD.
Alenius
Harri
H
Division of Immunology, Children's Hospital, Harvard Medical School, Massachusetts General Hospital, 02115, USA.
Laouini
Dhafer
D
Woodward
Amy
A
Mizoguchi
Emiko
E
Bhan
Atul K
AK
Castigli
Emanuela
E
Oettgen
Hans C
HC
Geha
Raif S
RS
D000485:Allergens / Q000276:immunology*; D000818:Animals; D006224:Cricetinae; D003876:Dermatitis, Atopic / Q000276:immunology*; D005260:Female; D007073:Immunoglobulin E / Q000097:blood*; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D010047:Ovalbumin / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D012867:Skin / Q000276:immunology*
D000485:Allergens; D012333:RNA, Messenger; D007073:Immunoglobulin E; D007371:Interferon-gamma; D010047:Ovalbumin