Graduate School of Science, University of Tokyo, Tokyo, Japan.
Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan.
Mucosal Immunol. 2018 May;11(3):763-773. doi: 10.1038/mi.2017.86. Epub 2017 Oct 25.
Dectin-1 (gene symbol: Clec7a) is a receptor for β-glucans that play an important role for the host defense against fungi. Recently, we showed that Clec7a mice are resistant against dextran sodium sulfate (DSS)-induced colitis because of regulatory T-cell population expansion in the colon. The regulatory T-cell expansion is caused by expansion of commensal Lactobacillus murinus whose growth is suppressed by an antimicrobial protein, calprotectin S100A8/A9. In this report, we showed that S100A8 was mainly produced by mouse colonic epithelial cells. S100A8 was not induced directly by Dectin-1 but by Dectin-1-induced cytokines, especially interleukin-17F (IL-17F), that were produced by several types of innate immune cells including CD11c/CD11b myeloid cells in colonic lamina propria. S100A8/A9 heterodimer preferentially suppressed the growth of L. murinus that was increased in both Clec7a and Il17f mice. Furthermore, similar expansion of L. murinus and DSS-colitis resistance were observed in mice fed with β-glucan-free food. These observations suggest that food-derived β-glucans control the specific commensal microbiota via the Dectin-1-IL-17F-calprotectin axis to maintain the intestinal homeostasis.
Dectin-1（基因符号：Cle c7a）是一种β-葡聚糖受体，在宿主防御真菌方面发挥着重要作用。最近，我们发现 Clec7a 小鼠对葡聚糖硫酸钠（DSS）诱导的结肠炎具有抗性，因为结肠中调节性 T 细胞群体扩张。调节性 T 细胞的扩张是由共生乳杆菌 Lactobacillus murinus 的扩张引起的，其生长受到抗菌蛋白 calprotectin S100A8/A9 的抑制。在本报告中，我们表明 S100A8 主要由小鼠结肠上皮细胞产生。S100A8 不是直接由 Dectin-1 诱导，而是由 Dectin-1 诱导的细胞因子诱导，特别是由包括结肠固有层中 CD11c/CD11b 髓样细胞在内的几种类型的固有免疫细胞产生的白细胞介素-17F（IL-17F）。S100A8/A9 异二聚体优先抑制在 Clec7a 和 Il17f 小鼠中增加的 L. murinus 的生长。此外，在喂食无β-葡聚糖食物的小鼠中也观察到类似的 L. murinus 扩张和 DSS-结肠炎抗性。这些观察结果表明，食物来源的β-葡聚糖通过 Dectin-1-IL-17F-calprotectin 轴控制特定的共生微生物群，以维持肠道内稳态。
