T-lymphocyte-induced, fas-mediated apoptosis is associated with early keratinocyte differentiation

Ilse Daehn, Antiopi Varelias, Timothy Rayner

    Research output: Contribution to journalArticlepeer-review

    8 Citations (Scopus)

    Abstract

    The development of eczematous lesions is thought to be due in part to a breakdown in skin barrier function as a result of T lymphocytes (T cells) invading the skin causing epidermal keratinocyte apoptosis. In this study, we investigated the interaction of T cells and keratinocytes on apoptosis and terminal differentiation using an in vitro co-culture system. Experiments were performed using the HaCaT keratinocyte cell line or normal human epidermal keratinocytes. Activated human peripheral blood-derived T cells were found to induce Fas-dependent keratinocyte apoptosis by up to sixfold. Increased Fas was associated with increased IFN-γ. The T-cell apoptotic signal was found to target preferentially keratinocytes in the very early stages of terminal differentiation, such as those with low levels of α6-integrin expression, and result in subsequent increased caspase 3 activity. This observation was accompanied by a marked increase in keratinocyte ICAM-1 expression and its ligand LFA-1 on T cells. Our data suggest that T cells may initiate the onset of keratinocyte terminal differentiation making them more susceptible to Fas-dependent cell death signals delivered by the T cells.

    Original languageEnglish
    Pages (from-to)372-380
    Number of pages9
    JournalExperimental Dermatology
    Volume19
    Issue number4
    DOIs
    Publication statusPublished - Apr 2010

    Keywords

    • Apoptosis
    • Cytokine
    • Differentiation
    • Fas
    • Keratinocyte

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