Loss of IDO1 Expression From Human Pancreatic β-Cells Precedes Their Destruction During the Development of Type 1 Diabetes.
Florence AnquetilGiada MondanelliNathaly GonzalezTeresa Rodriguez CalvoJose Zapardiel GonzaloLars KrogvoldKnut Dahl-JørgensenBenoit Van den EyndeCiriana OrabonaUrsula GrohmannMatthias G von HerrathPublished in: Diabetes (2018)
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.
Keyphrases
- type diabetes
- endothelial cells
- poor prognosis
- single cell
- glycemic control
- cardiovascular disease
- cell therapy
- systemic lupus erythematosus
- oxidative stress
- kidney transplantation
- adipose tissue
- pluripotent stem cells
- long non coding rna
- metabolic syndrome
- cell cycle arrest
- mesenchymal stem cells
- skeletal muscle
- cell proliferation
- insulin resistance
- signaling pathway
- wild type