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

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

doi:10.2337/db17-1281

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

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

Affiliations

¹ La Jolla Institute for Allergy and Immunology, La Jolla, CA.
² University of Perugia, Perugia, Italy.
³ Division of Paediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway.
⁴ Faculty of Dentistry, University of Oslo, Oslo, Norway.
⁵ de Duve Institute, Brussels, Belgium.
⁶ Ludwig Institute for Cancer Research, Brussels, Belgium.
⁷ La Jolla Institute for Allergy and Immunology, La Jolla, CA [email protected].
⁸ Novo Nordisk Diabetes Research & Development Center, Seattle, WA.

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.

Publication types

Comparative Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
Autoantibodies / metabolism
Autoimmune Diseases / immunology
Autoimmune Diseases / metabolism*
Autoimmune Diseases / pathology
Autoimmune Diseases / physiopathology
Autoimmunity*
Cadaver
Cohort Studies
Cross-Sectional Studies
Diabetes Mellitus, Type 1 / immunology
Diabetes Mellitus, Type 1 / metabolism*
Diabetes Mellitus, Type 1 / pathology
Diabetes Mellitus, Type 1 / physiopathology
Diabetes Mellitus, Type 2 / immunology
Diabetes Mellitus, Type 2 / metabolism
Diabetes Mellitus, Type 2 / pathology
Diabetes Mellitus, Type 2 / physiopathology
Disease Progression
Down-Regulation*
Female
Fluorescent Antibody Technique, Indirect
Humans
Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism*
Insulin / metabolism
Insulin-Secreting Cells / enzymology*
Insulin-Secreting Cells / immunology
Insulin-Secreting Cells / metabolism
Insulin-Secreting Cells / pathology
Male
Middle Aged
Prediabetic State / immunology
Prediabetic State / metabolism*
Prediabetic State / pathology
Prediabetic State / physiopathology
Protein Transport
Young Adult

Substances

Autoantibodies
IDO1 protein, human
Indoleamine-Pyrrole 2,3,-Dioxygenase
Insulin

Grants and funding

U01 AI102370/AI/NIAID NIH HHS/United States