Tackling autoimmunity with gene therapy.
Tackling autoimmunity with gene therapy.
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DOI：
10.4161/chim.22061
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发表时间：
2012-07-01
期刊：
影响因子：
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通讯作者：
Toh, Ban-Hock
中科院分区：
文献类型：
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作者：
Alderuccio, Frank;Toh, Ban-Hock
自身免疫性疾病由靶向自身组织的免疫系统的异常应答引起。我们对正常免疫发育的理解已经被用来颠覆这种自身反应性，并涉及将自身抗原暴露于发育中的免疫系统。这可以通过骨髓来源的细胞来实现，从而引入潜在的临床应用。我们已经使用多发性硬化症的小鼠模型来证明编码靶自身抗原的骨髓的转移可以用于促进免疫耐受。造血干细胞移植预处理受体的过程对于潜在的人类翻译至关重要。因此，我们已经直接解决了我们的模型是否也可以应用于非清髓性和毒性较小的调节，以促进耐受性和逆转已建立的疾病。我们迄今为止的研究表明，这确实是可以实现的，并且只需要低水平的嵌合体就可以实现耐受性。
Autoimmune diseases result from an aberrant response of the immune system that target self-tissues. Our understanding of normal immune development has been used to subvert this self-reactivity and involves exposing self-antigen to the developing immune system. This can be achieved through bone marrow derived cells, thus introducing potential clinical application. We have used the mouse model of multiple sclerosis to demonstrate that the transfer of bone marrow encoding a target autoantigen can be used to promote immune tolerance. The process of preconditioning recipients for hematopoietic stem cell transfer is critical for potential human translation. Thus, we have directly addressed if our model can also be applied in non-myeloablative and less toxic conditioning to promote tolerance and reverse established disease. Our studies to date indicate that this can indeed be achieved and that only low levels of chimerism are required to achieve tolerance.