Women's & Children's Health Research Institute, Women's and Children's Hospital, North Adelaide, SA, Australia.
Exp Dermatol. 2010 Apr;19(4):372-80. doi: 10.1111/j.1600-0625.2009.00917.x. Epub 2009 Jul 23.
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-gamma. 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 alpha 6-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.
特应性皮炎样皮损的发展部分归因于 T 淋巴细胞（T 细胞）侵入皮肤导致表皮角质形成细胞凋亡，使皮肤屏障功能受损。本研究采用体外共培养系统，研究 T 细胞与角质形成细胞在凋亡和终末分化方面的相互作用。实验采用 HaCaT 角质形成细胞系或正常人表皮角质形成细胞。结果发现，活化的人外周血源性 T 细胞可诱导 Fas 依赖性角质形成细胞凋亡，最高可达 6 倍。Fas 的增加与 IFN-γ的增加相关。T 细胞凋亡信号似乎优先针对终末分化早期的角质形成细胞，如那些 α6 整合素表达水平较低的细胞，导致随后 caspase 3 活性增加。这一观察结果伴随着角质形成细胞 ICAM-1 表达及其在 T 细胞上的配体 LFA-1 的显著增加。我们的数据表明，T 细胞可能启动角质形成细胞终末分化的发生，使它们更容易受到 T 细胞传递的 Fas 依赖性细胞死亡信号的影响。
