Regulatory T (Treg) cells expressing the transcription factor Foxp3 constitute a unique T-cell lineage committed to suppressive functions and play a central role in maintaining self-tolerance and immune homeostasis. While their differentiation state is remarkably stable in the face of various perturbations from the extracellular environment, recent studies have also revealed their adaptability to the changing environment; in response to extrinsic cues, Treg cells differentiate further into distinct substates to regulate different classes of immune responses effectively. In contrast, some other recent studies have challenged this notion of a committed Treg cell lineage and suggested that Treg cells might lose their identity and be reprogrammed to various effector helper T cells under certain circumstances, although this issue of environment-induced Treg cell reprogramming remains highly controversial. This review will focus on recent advances in our understanding of how the stability and adaptability of Treg cell lineage is regulated and how it might be perturbed in a changing environment.
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