Osteoprotegerin-dependent M cell self-regulation balances gut infection and immunity

Shunsuke Kimura, Yutaka Nakamura, Nobuhide Kobayashi, Katsuyuki Shiroguchi, Eiryo Kawakami, Mami Mutoh, Hiromi Takahashi-Iwanaga, Takahiro Yamada, Meri Hisamoto, Midori Nakamura, Nobuyuki Udagawa, Shintaro Sato, Tsuneyasu Kaisho, Toshihiko Iwanaga, Koji Hase

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)


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-κB 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.

Original languageEnglish
Article number234
JournalNature communications
Issue number1
Publication statusPublished - 2020 Dec 1

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry,Genetics and Molecular Biology
  • General
  • General Physics and Astronomy


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