Journal
NATURE IMMUNOLOGY
Volume 17, Issue 4, Pages 441-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.3345
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Funding
- Japan Society for the Promotion of Science (KAKENHI)
- Core Research for Evolutional Science and Technology
- Japan Agency for Medical Research and Development-Core Research for Evolutional Science and Technology
- Uehara Memorial Foundation
- Grants-in-Aid for Scientific Research [15H04862, 14J00739, 26293383, 15K15659, 26670575, 15H01365, 25293091] Funding Source: KAKEN
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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.
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