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Background: Asthma is an inflammatory airway disease associated with infiltration of T cells and eosinophils, increased levels of pro-inflammatory cytokines, and shedding of bronchial epithelial cells (EC). We have recently shown that T cells and eosinophils cooperate in inducing bronchial EC apoptosis in asthma through secretion of IFN-γ and TNF-α. Since EC shedding is a histologic hallmark of asthma, the intercellular junction of EC may be a target of pro-inflammatory cytokines. Methods: Bronchial EC, cultured and exposed to IFN-γ and TNF-α, were studied for the expression of adhesion molecules and apoptosis. In addition, the epithelial layer of bronchial biopsies from asthma patients was evaluated for apoptosis, shedding, and expression of adhesion molecules. Results: We demonstrate that the induction of EC apoptosis is accompanied by loss of E-cadherin. In situ examination of E-cadherin in asthma revealed a reduction in its expression on EC membranes. In contrast, the in vitro and in vivo expression of β1-integrins and intercellular adhesion molecule-1 (ICAM-1) increased on EC during asthmatic airway inflammation. Conclusions: Loss of cadherin-mediated intercellular adhesion and apoptosis could account for fragility and shedding of EC in asthma, especially since this occurs between columnar and basal EC. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Genetic predisposition and environmental instructions tune thresholds for the activation, effector functions and lifespan of T cells, other inflammatory cells and resident tissue cells. Defects in apoptosis and peripheral tolerance in T cells define different allergic phenotypes. In individuals with atopic allergic disease, activated allergen-specific T cells expressing high levels of IFN-γ predominantly undergo apoptosis in the circulation, skewing the immune response to surviving T helper type 2 (Th2) cells. In affected tissues, these cells switch on effector cytokines and induce the activation and apoptosis of epithelial cells. In individuals with non-atopic monoallergic disease, by contrast, a disturbed balance towards allergen-specific Th2 cells instead of T regulatory type 1 (Tr1) cells characterizes the T cell response. [Copyright &y& Elsevier]

Focuses on the apoptotic and antiapoptotic driving forces that play a role in the formation of eczema and maintenance and exacerbation of allergic inflammation in the skin of atopic dermatitis (AD) patients. Classification of the AD disease; Similarity among the majority of AD patients; Importance of apoptosis in physiological and pathological conditions.

Focuses on a study which explained the existence and activation of CD8+ T cells in eczema lesions contributing to immunoglobulin E production and eosinophil survival and development, chronicity and exacerbation of atopic dermatitis (AD). Classification of AD as a skin disease; Role played by T cells in both AD and contact dermatitis; Way in which additional evidence for in vivo activation of CLA+ T cells appears.

Recently we have shown that T-cell-mediated keratinocyte apoptosis plays a key pathogenetic role in the formation of eczematous dermatitis. Spongiosis, the histologic hallmark of eczematous dermatitis, is characterized by impairment of cohesion between epidermal keratinocytes. It is conceivable that the intercellular junction of keratinocytes is an early target of apoptosis-inducing T cells. In this study, we demonstrate that the induction of keratinocyte apoptosis is accompanied by a rapid cleavage of E-cadherin and loss of coimmunoprecipitated β-catenin. In situ examination of E-cadherin expression and cellular distribution in acute eczematous dermatitis revealed a reduction in keratinocyte membrane E-cadherin in areas of spongiosis. In contrast, the in vitro and in vivo expression of desmosomal cadherins during early apoptosis remained unchanged. Therefore, induction of keratinocyte apoptosis by skin-infiltrating T cells, subseqent cleavage of E-cadherin, and resisting desmosomal cadherins suggests a mechanism for spongiosis formation in eczematous dermatitis. [ABSTRACT FROM AUTHOR]