Peripherally induced regulatory T cells contribute to the control of autoimmune diabetes in the NOD mouse model

Eur J Immunol. 2018 Jul;48(7):1211-1216. doi: 10.1002/eji.201847498. Epub 2018 Apr 25.

Abstract

Type 1 diabetes (T1D) results from the autoimmune destruction of pancreatic beta cells and is partly caused by deficiencies in the Foxp3+ regulatory T-cell (Treg) compartment. Conversely, therapies that increase Treg function can prevent autoimmune diabetes in animal models. The majority of Tregs develop in the thymus (tTregs), but a proportion of Foxp3+ Tregs is generated in the periphery (pTregs) from Foxp3- CD4+ T-cell precursors. Whether pTregs play a distinct role in T1D has not yet been explored. We report here that pTregs are a key modifier of disease in the nonobese diabetic (NOD) mouse model for T1D. We generated NOD mice deficient for the Foxp3 enhancer CNS1 involved in pTreg induction. We show that CNS1 knockout decreased the frequency of pTregs and increased the risk of diabetes. Our results show that pTregs fulfill an important non-redundant function in the prevention of beta cell autoimmunity that causes T1D.

Keywords: CNS1; Foxp3; Type 1 diabetes; pTreg.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Diabetes Mellitus, Type 1 / immunology*
  • Forkhead Transcription Factors / metabolism
  • HSP72 Heat-Shock Proteins / genetics
  • Immunomodulation
  • Insulin-Secreting Cells / immunology*
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • Mice, Knockout
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes, Regulatory / immunology*
  • Thymus Gland / immunology*

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • HSP72 Heat-Shock Proteins