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

Author

Listed:
  • Jinxiu Rui

    (Yale University)

  • Songyan Deng

    (Yale University)

  • Ana Luisa Perdigoto

    (Yale University)

  • Gerald Ponath

    (Department of Neurology, Yale School of Medicine)

  • Romy Kursawe

    (The Jackson Laboratory for Genomic Medicine)

  • Nathan Lawlor

    (The Jackson Laboratory for Genomic Medicine)

  • Tomokazu Sumida

    (Department of Neurology, Yale School of Medicine)

  • Maya Levine-Ritterman

    (Department of Neurology, Yale School of Medicine)

  • Michael L. Stitzel

    (The Jackson Laboratory for Genomic Medicine
    University of Connecticut)

  • David Pitt

    (Department of Neurology, Yale School of Medicine)

  • Jun Lu

    (Yale University)

  • Kevan C. Herold

    (Yale University)

Abstract

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.

Suggested Citation

  • Jinxiu Rui & Songyan Deng & Ana Luisa Perdigoto & Gerald Ponath & Romy Kursawe & Nathan Lawlor & Tomokazu Sumida & Maya Levine-Ritterman & Michael L. Stitzel & David Pitt & Jun Lu & Kevan C. Herold, 2021. "Tet2 Controls the Responses of β cells to Inflammation in Autoimmune Diabetes," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25367-z
    DOI: 10.1038/s41467-021-25367-z
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