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1 型糖尿病与调节性 T 细胞。

Type 1 diabetes and T regulatory cells.

机构信息

Al-Azhar University, Cairo, Egypt.

Immunobiology & Transplantation Research, Houston Methodist Hospital, Texas Medical Center, 6670 Bertner Avenue, R7-211, Houston, TX 77030, United States.

出版信息

Pharmacol Res. 2015 Aug;98:22-30. doi: 10.1016/j.phrs.2015.04.009. Epub 2015 May 8.

Abstract

T-regulatory cells (Tregs) play a fundamental role in the creation and maintenance of peripheral tolerance. Deficits in the numbers and/or function of Tregs may be an underlying cause of human autoimmune diseases including type 1 Diabetes Mellitus (T1D), whereas an over-abundance of Tregs can hinder immunity against cancer or pathogens. The importance of Tregs in the control of autoimmunity is well established in a variety of experimental animal models. In mice, manipulating the numbers and/or function of Tregs can decrease pathology in a wide range of contexts, including autoimmunity and it is widely assumed that similar approaches will be possible in humans. T1D, the most prevalent human autoimmune disease, has been a focus of interventions either through direct and indirect in vivo proliferations or through adoptive transfer of the in vitro generated antigen specific and non specific Treg. Some challenges still need to be addressed, including a more specific phenotype marker for Tregs; the reproducibility of satisfactory animal results in human and the reconcile of discrepancies between in vitro and in vivo studies. In this article, we will highlight the role of Tregs in autoimmune disease in general with a special focus on T1D, highlighting progress made and challenges ahead in developing Treg-based therapies.

摘要

调节性 T 细胞(Tregs)在形成和维持外周耐受中发挥着重要作用。Tregs 数量和/或功能的缺陷可能是人类自身免疫性疾病(包括 1 型糖尿病(T1D))的根本原因,而 Tregs 的过度增加可能会阻碍对癌症或病原体的免疫。Tregs 在控制自身免疫方面的重要性在多种实验动物模型中得到了充分证实。在小鼠中,操纵 Tregs 的数量和/或功能可以降低多种情况下的病理学,包括自身免疫,人们普遍认为,类似的方法在人类中也是可行的。1 型糖尿病是最常见的人类自身免疫性疾病,一直是干预的焦点,无论是通过直接和间接的体内增殖,还是通过体外产生的抗原特异性和非特异性 Treg 的过继转移。仍需要解决一些挑战,包括 Tregs 的更特异性表型标志物;令人满意的动物结果在人类中的可重复性,以及体外和体内研究之间的差异的调和。在本文中,我们将重点介绍 Tregs 在一般自身免疫性疾病中的作用,特别关注 1 型糖尿病,强调在开发基于 Treg 的治疗方法方面取得的进展和面临的挑战。

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