Peroxisome-proliferator-activated receptor γ (PPARγ), B cell lymphoma 6 (BCL6), T-bet, GATA-binding protein 3 (GATA3), and RORγt regulate the differentiation and function of tissue Treg cells derived from eTreg and peripherally derived Treg (pTreg) cells. Treg cells expressing PPARγ, BCL6, or GATA3 mainly differentiate from tTreg cells, while RORγt+ Treg cells differentiate from naïve CD4+ T cells [34,35,36,43,44] and T-bet+ Treg cells likely differentiate from both eTreg and pTreg cells [45,46,47]. These tissue-specific Treg subsets express different functional molecules and play different roles in maintaining tissue homeostasis by suppressing specific immune responses and regulating lipid metabolism and tissue repair.