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Nat Immunol. 2016 Apr;17(4):441-50. doi: 10.1038/ni.3345. Epub 2016 Feb 8.

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

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Department of Immunology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
Life Science Center of Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba, Japan.
Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Kawaguch, Japan.
Japan Agency for Medical Research-Core Research for Evolutional Science and Technology, Japan Agency for Medical Research and Development, Tokyo, Japan.


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

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