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

Authors

  • Ilse S. Daehn,

    1. Women’s & Children’s Health Research Institute, Women’s and Children’s Hospital, North Adelaide, SA, Australia
    2. Department of Medicine, The Flinders University of South Australia, Bedford Park, SA, Australia
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  • Antiopi Varelias,

    1. Women’s & Children’s Health Research Institute, Women’s and Children’s Hospital, North Adelaide, SA, Australia
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  • Timothy E. Rayner

    1. Women’s & Children’s Health Research Institute, Women’s and Children’s Hospital, North Adelaide, SA, Australia
    2. Department of Medicine, The Flinders University of South Australia, Bedford Park, SA, Australia
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Dr I. Daehn, Cancer Research UK, Mammalian DNA Repair, Clare Hall Laboratories, Blanche Lane, South Mimms, EN6 3LD Hertfordshire, UK, Tel.: (+44) 0170 762 5883, Fax: (+44) 0207 269 3801, e-mail: ilse.daehn@cancer.org.uk

Abstract

Please cite this paper as: T-lymphocyte-induced, fas-mediated apoptosis is associated with early keratinocyte differentiation. Experimental Dermatology 2009.

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.

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