No eczema without keratinocyte death.

Eczematous dermatitis comprises a heterogenous group of inflammatory skin diseases characterized by a typical morphological reaction pattern. In the acute stage, the typical clinical features include itching, redness, papules, and vesicles associated with exudation. The two most frequent reasons for an eczematous reaction are atopic dermatitis (AD) and allergic contact dermatitis (ACD). Although AD and ACD are completely different in nature and pathogenetically unrelated, both disorders in the acute stage share common morphological features, especially vesicle formation, which ultimately causes a disruption of the epidermal barrier. The loss of this protective shield allows additional external noxious agents of microbial, chemical, or physical origin to enter the skin and to aggravate and to perpetuate the disease. Hence, vesicle formation and subsequent loss of the epidermal barrier is a key event in acute eczematous reactions. Histopathologically, eczematous reactions are characterized by a mononuclear infiltrate with an intercellular epidermal edema, a condition called spongiosis. Severe spongiosis causes keratinocytes’ intercellular attachments to rupture and is regarded as the major culprit in generating vesicles in acute eczematous dermatitis (1). In this issue of the JCI, however, Trautmann et al. (2) provide evidence that another pathway, induction of apoptosis of keratinocytes via activation of the Fas receptor system, also disrupts the epidermal barrier, and they argue that infiltrating T lymphocytes are the direct cause of keratinocyte death through this novel pathway. Cell death by apoptosis is a tightly regulated process that enables removal of unnecessary, aged, or damaged cells. During apoptosis a complex death program becomes initiated that ultimately leads to the fragmentation of the cell, finally breaking it up into membrane-enclosed bodies that are phagocytosed by macrophages. Because it does not involve the release of inflammatory mediators, apoptosis, in sharp contrast to necrosis, does not typically provoke an inflammatory reaction. Nevertheless, inflammation can induce local apoptosis, and apoptosis-associated inflammation is seen in such conditions as viral hepatitis and Hashimoto’s thyroiditis, as well as eczematous dermatitis. One way to induce apoptosis is by triggering a family of transmembrane proteins called death receptors (3), of which the Fas protein (CD95) may be the most important (4), since Fasinduced apoptosis appears to be