Osteoprotegerin-dependent M cell self-regulation balances gut infection and immunity
Osteoprotegerin-dependent M cell self-regulation balances gut infection and immunity
复制标题
DOI：
10.1038/s41467-019-13883-y
复制
发表时间：
2020-01-13
影响因子：
16.6
通讯作者：
Hase, Koji
中科院分区：
文献类型：
--
作者：
Kimura, Shunsuke;Nakamura, Yutaka;Hase, Koji
微折叠细胞（M细胞）负责抗原摄取，以启动肠道相关淋巴组织（GALT）中的免疫应答。核因子-κ B配体受体激活因子（RANKL）是M细胞分化所必需的。滤泡相关上皮（FAE）覆盖GALT，并持续暴露于FAE下方基质细胞的RANKL，但只有一部分FAE细胞分化为M细胞。在这里，我们表明，M细胞表达骨保护素（OPG），RANKL的可溶性抑制剂，抑制相邻的FAE细胞分化成M细胞。值得注意的是，OPG缺乏增加了GALT中的M细胞数量，并增强了肠道细菌特异性免疫球蛋白的产生，从而改善了实验性结肠炎小鼠的疾病症状。相比之下，OPG缺陷小鼠对沙门氏菌感染高度敏感。因此，OPG依赖的M细胞分化的自我调节对于感染风险和在粘膜表面执行免疫监视的能力之间的平衡是必不可少的。
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.