Apoptotic epithelial cells control the abundance of T sub(reg) cells at barrier surfaces

Epithelial tissues continually undergo apoptosis. Commensal organisms that inhabit the epithelium influence tissue homeostasis, in which regulatory T cells (T sub(reg) cells) have a central role. However, the physiological importance of epithelial cell apoptosis and how the number of T sub(reg) cells is regulated are both incompletely understood. Here we found that apoptotic epithelial cells negatively regulated the commensal-stimulated proliferation of T sub(reg) cells. Gut commensals stimulated CX3CR1 super(+)CD103 super(-)CD11b super(+) dendritic cells (DCs) to produce interferon- beta (IFN- beta ), which augmented the proliferation of T sub(reg) cells in the intestine. Conversely, phosphatidylserine exposed on apoptotic epithelial cells suppressed IFN- beta production by the DCs via inhibitory signaling mediated by the cell-surface glycoprotein CD300a and thus suppressed T sub(reg) cell proliferation. Our findings reveal a regulatory role for apoptotic epithelial cells in maintaining the number of T sub(reg) cell and tissue homeostasis.