Engagement of the α2β1 integrin inhibits Fas ligand expression and activation-induced cell death in T cells in a focal adhesion kinase-dependent manner
Engagement of the α2β1 integrin inhibits Fas ligand expression and activation-induced cell death in T cells in a focal adhesion kinase-dependent manner
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DOI：
10.1182/blood.v95.6.2044
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发表时间：
2000-03-15
期刊：
影响因子：
20.3
通讯作者：
Vuori, K
中科院分区：
文献类型：
--
作者：
Aoudjit, F;Vuori, K
T细胞受体（TCR）介导的细胞凋亡，也称为活化诱导的细胞死亡（AICD），在免疫应答的控制和T细胞库的发育中起重要作用。从机制上讲，AICD在很大程度上归因于活化T细胞中Fas配体（Fas-L）与其细胞表面受体Fas的相互作用。由细胞粘附受体的整联蛋白家族介导的信号转导先前已显示在许多不同细胞类型中调节凋亡;在T细胞中，已知整联蛋白信号传导通过提供TCR的共刺激信号，在这项研究中，我们证明了通过胶原受体α 2 β 1整合素的信号传导通过抑制Fas-1特异性抑制AICD。L在活化的Jurkat T细胞中的表达。α 2 β 1整联蛋白与单克隆抗体或α 2 β 1的同源配体i型胶原蛋白的结合，分别使抗CD 3和PMA/离子霉素诱导的细胞死亡减少了30%和40%，并使Fas-L mRNA的表达减少了50%。进一步的研究表明，α 2 β 1介导的AICD和Fas-L表达的抑制需要粘着斑激酶FAK，一种整合素信号通路中的已知组分。这些结果表明α 2 β 1整联蛋白在控制免疫应答和T细胞发育的稳态中的作用，（C）2000年由美国血液学会发表。
T-cell receptor (TCR)-mediated apoptosis, also known as activation-induced cell death (AICD), plays an important role in the control of immune response and in the development of T-cell repertoire. Mechanistically, AICD has been largely attributed to the interaction of Fas ligand (Fas-L) with its cell surface receptor Fas In activated T cells. Signal transduction mediated by the integrin family of cell adhesion receptors has been previously shown to modulate apoptosis in a number of different cell types; in T cells, integrin signaling is known to be important in cellular response to antigenic challenge by providing a co-stimulatory signal for TCR, In this study we demonstrate that signaling via the collagen receptor alpha 2 beta 1 integrin specifically inhibits AICD by inhibiting Fas-L expression in activated Jurkat T cells. Engagement of the alpha 2 beta 1 integrin with monoclonal antibodies or with type i collagen, a cognate ligand for alpha 2 beta 1, reduced anti-CD3 and PMA/ionomycin-induced cell death by 30% and 40%, respectively, and the expression of Fas-L mRNA by 50%. Further studies Indicated that the alpha 2 beta 1-mediated inhibition of AICD and Fas-L expression required the focal adhesion kinase FAK, a known component in the integrin signaling pathways. These results suggest a role for the alpha 2 beta 1 integrin in the control of homeostasis of Immune response and T-cell development, (C) 2000 by The American Society of Hematology.