Authors: 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
Published: 2020-01-13
DOI: 10.1038/s41467-019-13883-y
Source: Full article
AbstractMicrofold 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 toSalmonellainfection. 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.