Apoptotic epithelial cells control the abundance of Treg cells at barrier surfaces

Epithelial tissues continually undergo apoptosis. Commensal organisms that inhabit the epithelium influence tissue homeostasis, in which regulatory T cells (T-reg cells) have a central role. However, the physiological importance of epithelial cell apoptosis and how the number of T-reg cells is regulated are both incompletely understood. Here we found that apoptotic epithelial cells negatively regulated the commensal-stimulated proliferation of T-reg cells. Gut commensals stimulated CX3CR1(+)CD103(-)CD11b(+) dendritic cells (DCs) to produce interferon-beta (IFN-beta), which augmented the proliferation of T-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-reg cell proliferation. Our findings reveal a regulatory role for apoptotic epithelial cells in maintaining the number of T-reg cell and tissue homeostasis.