Document Type

Article

Publication Date

8-20-2021

Publication Title

Nat Commun

Keywords

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

JAX Source

Nat Commun 2021 Aug 20; 12(1):5074

Volume

12

Issue

1

First Page

5074

Last Page

5074

ISSN

2041-1723

PMID

34417463

DOI

https://doi.org/10.1038/s41467-021-25367-z

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.

Comments

This article is licensed under a Creative Commons Attribution 4.0 International License.

Download

Share

COinS