In:
The Journal of Immunology, The American Association of Immunologists, Vol. 175, No. 2 ( 2005-07-15), p. 1286-1294
Abstract:
Skin inflammation in atopic dermatitis starts with Th2 and IgE-mediated responses against exogenous allergens and, for unknown reasons, resembles features of a Th1-driven reaction in the chronic stages. We report the characterization of a human protein, Hom s 4, recognized by IgE autoantibodies from atopic dermatitis patients. The complete Hom s 4 cDNA codes for a 54-kDa basic protein containing two typical calcium-binding domains separated by an unusually long α-helical domain. Therefore, Hom s 4 and homologous proteins found by sequence comparison in mice, fruit flies, and nematodes constitute a novel subfamily of calcium-binding proteins. Using Hom s 4-specific Abs, it is demonstrated that the protein is strongly expressed within epidermal keratinocytes and dermal endothelial cells. Purified Hom s 4 showed IgE cross-reactivity with exogenous calcium-binding allergens from plants and fish but, in contrast to the exogenous allergens, induced only weak histamine release from patient basophils. However, the analysis of Hom s 4-specific cytokine and humoral immune responses indicated that Hom s 4 strongly induces Th1 responses which are accompanied by the release of IFN-γ, a cytokine implicated in epithelial cell damage. Hom s 4-induced IFN-γ production was found in normal individuals, in patients with chronic inflammatory skin diseases and in Th2-prone atopic persons, suggesting that Hom s 4 represents a protein with an intrinsic property to induce Th1-mediated autoreactivity. It may thus contribute to chronic skin inflammation in atopic as well as in nonatopic persons.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.175.2.1286
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2005
detail.hit.zdb_id:
1475085-5
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