ArticleProceedings of the National Academy of Sciences of the United States of America2016
Nuclear transfer nTreg model reveals fate-determining TCR-β and novel peripheral nTreg precursors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed, 3 citations in OpenAlex.
- Premature Activation of Immune Transcription Programs in Autoimmune-Predisposed Mouse Embryonic Stem Cells and Blastocysts.International journal of molecular sciences · 2020Article
- Prediabetes Induced by a Single Autoimmune B Cell Clone.Frontiers in immunology · 2020Article
- Deconstructive somatic cell nuclear transfer reveals novel regulatory T-cell subsets.The Journal of allergy and clinical immunology · 2018Article
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9 authors at 1 institution in 1 country.
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Abstract
To study the development and function of "natural-arising" T regulatory (nTreg) cells, we developed a novel nTreg model on pure nonobese diabetic background using epigenetic reprogramming via somatic cell nuclear transfer. On RAG1-deficient background, we found that monoclonal FoxP3(+)CD4(+)Treg cells developed in the thymus in the absence of other T cells. Adoptive transfer experiments revealed that the thymic niche is not a limiting factor in nTreg development. In addition, we showed that the T-cell receptor (TCR) β-chain of our nTreg model was not only sufficient to bias T-cell development toward the CD4 lineage, but we also demonstrated that this TCR β-chain was able to provide stronger TCR signals. This TCR-β-driven mechanism would thus unify former per se contradicting hypotheses of TCR-dependent and -independent nTreg development. Strikingly, peripheral FoxP3(-)CD4(+)T cells expressing the same TCR as this somatic cell nuclear transfer nTreg model had a reduced capability to differentiate into Th1 cells but were poised to differentiate better into induced nTreg cells, both in vitro and in vivo, representing a novel peripheral precursor subset of nTreg cells to which we refer to as pre-nTreg cells.
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