Tet2 Controls the Responses of β cells to Inflammation in Autoimmune Diabetes

Nat Commun. 2021 Aug 20;12(1):5074. doi: 10.1038/s41467-021-25367-z.


β cells may participate and contribute to their own demise during Type 1 diabetes (T1D). Here we report a role of their expression of Tet2 in regulating immune killing. Tet2 is induced in murine and human β cells with inflammation but its expression is reduced in surviving β cells. Tet2-KO mice that receive WT bone marrow transplants develop insulitis but not diabetes and islet infiltrates do not eliminate β cells even though immune cells from the mice can transfer diabetes to NOD/scid recipients. Tet2-KO recipients are protected from transfer of disease by diabetogenic immune cells.Tet2-KO β cells show reduced expression of IFNγ-induced inflammatory genes that are needed to activate diabetogenic T cells. Here we show that Tet2 regulates pathologic interactions between β cells and immune cells and controls damaging inflammatory pathways. Our data suggests that eliminating TET2 in β cells may reduce activating pathologic immune cells and killing of β cells.

Publication types

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

MeSH terms

  • Animals
  • Base Sequence
  • Cytotoxicity, Immunologic
  • DNA-Binding Proteins / metabolism*
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / pathology*
  • Dioxygenases
  • Disease Progression
  • Female
  • Humans
  • Immunity
  • Inflammation / genetics
  • Inflammation / pathology*
  • Insulin-Secreting Cells / metabolism*
  • Insulin-Secreting Cells / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • Proto-Oncogene Proteins / metabolism*
  • T-Lymphocytes / immunology
  • Transcription, Genetic


  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • Dioxygenases
  • TET2 protein, human
  • Tet2 protein, mouse