Journal
NATURE COMMUNICATIONS
Volume 11, Issue 1, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-019-13883-y
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Funding
- MEXT [25460261, 16K08457, 18H06033, 16H01369, 17H04089, 18H04680, 25293114, 26116709]
- AMED-Crest [16gm0000000h0101, 17gm1010004h0102, 18gm1010004h0103, 19gm1010004s0104]
- JST PRESTO [JPMJPR19H3]
- Research Foundation for Opto-Science and Technology
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- Food Science Institute Foundation
- SENSHIN Medical Research Foundation
- Takeda Science Foundation
- NOVARTIS Foundation JAPAN for Promotion of Science
- Grant for Joint Research Project of the Institute of Medical Science, the University of Tokyo
- JSPS [25460261, 16K08457, 18H06033, 16H01369, 17H04089, 18H04680, 25293114, 26116709]
- Grants-in-Aid for Scientific Research [25293114, 17H04089, 26116709, 16K08457, 16H01369, 18H04680, 25460261, 18H06033] Funding Source: KAKEN
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Microfold cells (M cells) are responsible for antigen uptake to initiate immune responses in the gut-associated lymphoid tissue (GALT). Receptor activator of nuclear factor-kappa B ligand (RANKL) is essential for M cell differentiation. Follicle-associated epithelium (FAE) covers the GALT and is continuously exposed to RANKL from stromal cells underneath the FAE, yet only a subset of FAE cells undergoes differentiation into M cells. Here, we show that M cells express osteoprotegerin (OPG), a soluble inhibitor of RANKL, which suppresses the differentiation of adjacent FAE cells into M cells. Notably, OPG deficiency increases M cell number in the GALT and enhances commensal bacterium-specific immunoglobulin production, resulting in the amelioration of disease symptoms in mice with experimental colitis. By contrast, OPG-deficient mice are highly susceptible to Salmonella infection. Thus, OPG-dependent self-regulation of M cell differentiation is essential for the balance between the infectious risk and the ability to perform immunosurveillance at the mucosal surface.
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