JGM, Animals, Base Sequence, Cytotoxicity, Immunologic, DNA-Binding Proteins, Diabetes Mellitus, Type 1, Disease Progression, Female, Humans, Immunity, Inflammation, Insulin-Secreting Cells, Mice, Inbred C57BL, Mice, Inbred NOD, Proto-Oncogene Proteins, T-Lymphocytes, Transcription, Genetic
Nat Commun 2021 Aug 20; 12(1):5074
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.
Rui, Jinxiu; Deng, Songyan; Perdigoto, Ana Luisa; Ponath, Gerald; Kursawe, Romy; Lawlor, Nathan; Sumida, Tomokazu; Levine-Ritterman, Maya; Stitzel, Michael L.; Pitt, David; Lu, Jun; and Herold, Kevan C, "Tet2 Controls the Responses of β cells to Inflammation in Autoimmune Diabetes." (2021). Faculty Research 2021. 174.