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IDO1 表达缺失的人胰岛β细胞在 1 型糖尿病发生时会发生破坏。

Loss of IDO1 Expression From Human Pancreatic β-Cells Precedes Their Destruction During the Development of Type 1 Diabetes.

机构信息

La Jolla Institute for Allergy and Immunology, La Jolla, CA.

University of Perugia, Perugia, Italy.

出版信息

Diabetes. 2018 Sep;67(9):1858-1866. doi: 10.2337/db17-1281. Epub 2018 Jun 26.

Abstract

Indoleamine 2,3 dioxygenase-1 (IDO1) is a powerful immunoregulatory enzyme that is deficient in patients with type 1 diabetes (T1D). In this study, we present the first systematic evaluation of IDO1 expression and localization in human pancreatic tissue. Although IDO1 was constitutively expressed in β-cells from donors without diabetes, less IDO1 was expressed in insulin-containing islets from double autoantibody-positive donors and patients with recent-onset T1D, although it was virtually absent in insulin-deficient islets from donors with T1D. Scatter plot analysis suggested that IDO1 decay occurred in individuals with multiple autoantibodies, prior to β-cell demise. IDO1 impairment might therefore contribute to β-cell demise and could potentially emerge as a promising therapeutic target.

摘要

吲哚胺 2,3 双加氧酶-1(IDO1)是一种强大的免疫调节酶,在 1 型糖尿病(T1D)患者中缺乏。在这项研究中,我们首次对 IDO1 在人胰腺组织中的表达和定位进行了系统评估。尽管 IDO1 在无糖尿病供体的β细胞中持续表达,但来自双重自身抗体阳性供体和近期发病的 T1D 患者的含胰岛素胰岛中 IDO1 的表达较少,尽管在 T1D 供体胰岛素缺乏的胰岛中几乎不存在。散点图分析表明,IDO1 的衰减发生在存在多种自身抗体的个体中,早于β细胞死亡之前。因此,IDO1 损伤可能导致β细胞死亡,并可能成为有前途的治疗靶点。

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