Mast cells are one major source of interleukin-4 in atopic dermatitis

Abstract

Several reports have shown the presence of T-helper lymphocytes with Th2 characteristics in the skin lesions of atopic dermatitis (AD). However, Th2 cells themselves require an exogenous pulse of IL-4 to initiate their differentiation and synthesis of IL-4. As mast cells have recently been shown to contain IL-4, this finding prompted us to investigate IL-4 in mast cells of AD lesions, to determine if they might provide the IL-4 pulse needed by the Th2 cells. In this study, we measured IL-4 immunoreactivity in mast cells of non-lesional and lesional skin sections from 20 patients with AD. Ten patients with nummular eczema (NE) without any atopic features or background, and five healthy subjects, served as the control groups. Mast cells were first identified using an enzyme--histochemical staining method for tryptase. Subsequently, the sections were photographed, the tryptase stain was removed, and IL-4 was demonstrated with a polyclonal antibody. The sections were photographed again, and the percentage of IL-4 positive mast cells was calculated. The percentage of mast cells exhibiting IL-4 immunoreactivity in the upper dermis in lesional vs. non-lesional skin was 66 +/- 18% vs. 37 +/- 18% in AD (P < 0.0001, paired t-test), but only 46 +/- 19% vs. 31 +/- 22% in NE. In the skin of healthy controls, only 23 +/- 25% of the mast cells were positive for IL-4. In addition, a significant difference was found between lesional skin of AD vs. NE patients (P < 0.008, unpaired t-test).(ABSTRACT TRUNCATED AT 250 WORDS)

L-Selectin or ICAM-1 Deficiency Reduces an Immediate-Type Hypersensitivity Response by Preventing Mast Cell Recruitment in Repeated Elicitation of Contact Hypersensitivity

“…Immunohistochemical analysis has shown that Th2-type cytokines, especially IL-4, are predominantly produced by mast cells and CD4 ϩ T cells in this chronic CH model (11). Consistent with this, mast cells are one of the major sources of IL-4 in lesional skin from patients with AD (37). Therefore, the results of this study suggest that L-selectin and ICAM-1 regulate IgE production indirectly by controlling mast cell accumulation at sites of inflammation.…”

Atopic dermatitis: from the genes to skin lesions

“…Mitosis of mast cells has been observed in AD lesions (74), suggesting a pathophysiologic role for mast cells in this disease. Furthermore, it has been shown that mast cells may be an initial source of IL-4 in the lesions, a cytokine which may drive the lesional T cells in a Th2 direction (75). An increased number of tryptase-positive mast cells lacking anti-in¯ammatory chymase activity have been demonstrated in nonlesional skin of AD and nummular eczema (76), and may be linkable to the mast-cell tryptase proposed as a candidate gene for AD.…”

Does allergy impair innate immunity? Leads and lessons from atopic dermatitis

“…Mast cells may be a major source of Th2 cytokines in AD (16), and mast cell-derived mediators may inhibit antimicrobial peptide secretion (75). Thus, in theory, targeting mast cells may allow for a down-regulation of Th2 skewing (which would be beneficial for the course of allergic conditions) and for restoring Th1 cytokine and antimicrobial peptide patterns, which in turn would improve innate immunity.…”

“…addition, mast cells are thought to contribute to the Th2 phenotype because 60% of them are IL-4 producers (16). Mast cells may also release substantial amounts of selective Th2 cytokines in response to IL-1 and the epithelial-derived cytokine thymic stromal lymphopoietin (TSLP), which is profoundly expressed by keratinocytes in atopic dermatitis.…”