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

在 1 型糖尿病的发展过程中,人类胰腺 β 细胞中 IDO1 表达的丧失先于其被破坏

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作者:Florence Anquetil, Giada Mondanelli, Nathaly Gonzalez, Teresa Rodriguez Calvo, Jose Zapardiel Gonzalo, Lars Krogvold, Knut Dahl-Jørgensen, Benoit Van den Eynde, Ciriana Orabona, Ursula Grohmann, Matthias G von Herrath

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.

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