Model of T cell trafficking in peripheral tissues impacting the generation of T_RM cells. Multiple factors can influence the decision of effector T cells (T_EFF) to enter inflamed tissues, return to the circulation, or remain locally and differentiate into T_RM cells. Local T cell retention is classically achieved via the downregulation of tissue egress molecules, including CCR7 and S1PRs. In this study, we identified S1PR5 as an additional regulator of these decisions, with S1PR5 expression limiting T cell extravasation and promoting T cell egress, thereby impeding T_RM cell development. While S1PR1 and S1PR5 share the same ligand, these two receptors are controlled by distinct transcriptional regulators, with KLF2 and ZEB2 being the main drivers of S1PR1 and S1PR5, respectively. Importantly, despite exhibiting distinct transcriptional regulation, the tissue-derived cytokine TGF-β promotes downregulation of both pathways and ultimately S1pr1 and S1pr5, thereby enforcing tissue retention and T_RM cell differentiation. T_CIRC, circulating T cell.