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CD4+ Foxp3+ T Regulatory (Treg) cells play a critical role in the homeostasis and maintenance of the immune system. The understanding of different aspects of Treg cells biology remains an intensively investigated subject as altering their generation, stability, or function by drugs or biologics may have therapeutic value in the treatment of autoimmune and inflammatory diseases as well as cancers. This review will focus on recent studies on the role of cytokines, T Cell Receptor (TCR) and co-stimulatory/co-inhibitory molecules signaling, location and metabolism on the homeostasis and stability of Treg cells. The potential for therapeutic manipulation of each of these factors will be discussed.…