Development and function of FOXP3+ regulators of immune responses

A subset of CD4+ T cells, recognized as FOXP3+ regulatory T (Treg) cells, are involved in preserving immune tolerance. Defects in these cells drive the pathogenesis of autoimmune diseases. In this review, we discuss the functions and dysfunctions in the developmental pathways of FOXP3+ Tregs, their emerging roles, and explore potential therapeutic targets. The Forkhead Box P3 (FOXP3) protein is an essential transcription factor for the development and function of regulatory T cells (Tregs), involved in the maintenance of immunological tolerance. Although extensive research over the last decade has investigated the critical role of FOXP3(+) cells in preserving immune homeostasis, our understanding of their specific functions remains limited. Therefore, unveiling the molecular mechanisms underpinning the up- and downstream transcriptional regulation of and by FOXP3 is crucial for developing Treg-targeted therapeutics. Dysfunctions in FOXP3(+) Tregs have also been found to be inherent drivers of autoimmune disorders and have been shown to exhibit multifaceted functions in the context of cancer. Recent research suggests that these cells may also be involved in tissue-specific repair and regeneration. Herein, we summarize current understanding of the thymic-transcriptional regulatory landscape of FOXP3(+) Tregs, their epigenetic modulators, and associated signaling pathways. Finally, we highlight the contributions of FOXP3 on the functional development of Tregs and reflect on the clinical implications in the context of pathological and physiological immune responses.

Automated summary

This review discusses the functions and dysfunctions in the developmental pathways of FOXP3+ regulatory T cells (Tregs), their emerging roles, and potential therapeutic targets. The transcription factor FOXP3 is crucial for the development and function of Tregs, which maintain immune tolerance. Dysfunctions in FOXP3+ Tregs are implicated in autoimmune diseases and exhibit multifaceted functions in cancer. Recent studies also suggest their involvement in tissue-specific repair and regeneration. Understanding the molecular mechanisms and clinical implications of FOXP3 is important for developing Treg-targeted therapies.