Exposing unstable regulatory T cells

Abstract

T Cells The regulatory T cell (Treg) gene expression program is stably maintained by the transcription factor Foxp3, although certain environmental signals can trigger loss of Foxp3 expression and acquisition of an effector phenotype. Using genetic fate mapping and adoptive transfers in mice, Junius et al. demonstrate that fate instability is limited to a subset of Tregs that can be purged through serial exposure to a lymphopenic environment. Tregs lacking neuropilin-1 (Nrp1) expression and displaying a naive phenotype were transcriptionally related to progeny that had recently lost Foxp3 expression. Nrp1-negative Tregs were then enriched for unstable Tregs upon lymphopenic challenge. These results demonstrate that Foxp3-positive cells are heterogeneous in their commitment to the Treg lineage, which could be applied to improve the stability of Treg-based cell therapies. Sci. Immunol. 6 , eabe4723 (2021).