Unstable FoxP3+ T regulatory cells in NZW mice

Proceedings of the National Academy of Sciences of the United States of America
Fabien DépisChristophe Benoist

Abstract

Regulatory T (Treg) cells that express the transcription factor FoxP3 play a key role in self-tolerance and the control of inflammation. In mice and humans, there is a wide interindividual range in Treg frequency, but little is known about the underlying genetic or epigenetic mechanisms. We explored this issue in inbred strains of mice, with a special focus on the low proportion of Treg cells found in NZW mice. Mixed bone marrow chimera experiments showed this paucity to be intrinsic to NZW Treg cells, a dearth that could be tied to poor stability of the Treg pool and of FoxP3 expression. This instability was not a consequence of differential epigenetic marks, because Treg-specific CpG hypomethylation profiles at the Foxp3 locus were similar in all strains tested. It was also unrelated to the high expression of IFN signature genes in NZW, as shown by intercross to mice with an Ifnar1 knockout. NZW Tregs were less sensitive to limiting doses of trophic cytokines, IL-2 and -33, for population homeostasis and for maintenance of FoxP3 expression. Gene-expression profiles highlighted specific differences in the transcriptome of NZW Tregs compared with those of other strains, but no single defect could obviously account for the insta...Continue Reading

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May 18, 2016·Proceedings of the National Academy of Sciences of the United States of America·Stefan O ReberChristopher A Lowry
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Apr 27, 2021·Frontiers in Immunology·Xundong WeiXuyu Zhou
Jun 2, 2021·Cellular & Molecular Immunology·Peter LehmkuhlAlla Skapenko

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