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.

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
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Insulin
  • indoleamine 2,3-dioxygenase 1, human