Research ArticleT CELL DIFFERENTIATION

Helios enhances the preferential differentiation of human fetal CD4+ naïve T cells into regulatory T cells

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Science Immunology  22 Nov 2019:
Vol. 4, Issue 41, eaav5947
DOI: 10.1126/sciimmunol.aav5947

Helios lights the way to immunotolerance

Fetal naïve T cells are more apt than their adult counterparts to differentiate into regulatory T (Treg) cells after stimulation through the T cell receptor. Ng et al. investigated the origin of this bias using transcriptional and epigenetic profiling to compare fetal and adult naïve T cells with induced Treg cells. Expression of the Treg-associated transcription factor Helios by most fetal naïve T cells, but not adult naïve T cells, suggested that Helios might have a key role. CRISPR-Cas9–mediated deletion of Helios in fetal naïve T cells impaired their ability to differentiate into induced Treg cells in the absence of exogenous TGF-β. These findings lay the groundwork for development of new translational approaches to coax adult naïve T cells to differentiate into stable Treg cells.

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