Regulatory T Cells: the Many Faces of Foxp3

The document from 2019 reviews the role of the transcription factor Foxp3 in the biology of regulatory T (Treg) cells, which are essential for maintaining immune balance and preventing autoimmunity. It discusses how Foxp3 acts as a transcriptional modulator and metabolic gatekeeper for Treg cells, and how mutations in FOXP3 can lead to immune dysregulation disorders. The review also covers the differentiation of Treg cells, their epigenetic regulation, and the impact of other Fox transcription factors on Treg cell function. It highlights the importance of CTLA-4 in Treg cell-mediated suppression and the role of Treg cells in tissue adaptation and hair follicle regeneration. The document further explores Treg cell plasticity and their pathological reprogramming in chronic inflammatory diseases, suggesting that therapeutic interventions targeting Treg cell reprogramming and metabolic pathways could restore immune tolerance. It concludes with the potential of precision immunotherapy targeting Treg cells for treating autoimmune and non-immune disorders, mentioning clinical benefits of low-dose IL-2 therapy and the future potential of rapamycin and gene editing. The work was supported by the National Institutes of Health grants.