The differential fate of cadherins during T-cell-induced keratinocyte apoptosis leads to spongiosis in eczematous dermatitis

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 imp airment of cohesion between epidermal keratinocytes. It is conceivable that the intercellular junction of keratinocytes is an early target of apoptosi s-inducing T cells. In this study, we demonstrate that the induction of ker atinocyte apoptosis is accompanied by a rapid cleavage of E-cadherin and lo ss of coimmunoprecipitated beta -catenin. In situ examination of E-cadherin expression and cellular distribution in acute eczematous dermatitis reveal ed a reduction in keratinocyte membrane E-cadherin in areas of spongiosis. In contrast, the in vitro and in vivo expression of desmosomal cadherins du ring early apoptosis remained unchanged. Therefore, induction of keratinocy te apoptosis by skin-infiltrating T cells, subseqent cleavage of E-cadherin , and resisting desmosomal cadherins suggests a mechanism for spongiosis fo rmation in eczematous dermatitis.