Interdisciplinary Graduate School of Agriculture and Engineering, University of Miyazaki, Miyazaki, Japan.
Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
Comp Biochem Physiol Part D Genomics Proteomics. 2021 Dec;40:100885. doi: 10.1016/j.cbd.2021.100885. Epub 2021 Jul 26.
The mutual relationship between the intestinal immune system and the gut microbiota has received a great deal of attention. In mammals, interleukin-17A and F (IL-17A/F) are inflammatory cytokines and key regulators of the gut microbiota. However, in teleosts, the function of IL-17A/F in controlling the gut microbiota is poorly understood. We attempted to elucidate the importance of teleost IL-17 signaling in controlling gut microbiota. We previously established a knockout (KO) of IL-17 receptor A (RA) 1, a receptor for IL-17A/F, in the Japanese medaka (Oryzias latipes) using the CRISPR-Cas9 system and performed 16S rRNA-based metagenomic analyses using the anterior and posterior sections of the intestinal tract. The number of observed OTUs in the anterior intestine was significantly decreased in IL-17RA1 KO medaka compared to that in the wild-type (WT). Furthermore, β-diversity analysis (weighted UniFrac) revealed considerably different bacterial composition in the anterior intestine of IL-17RA1 KO compared to WT, with similar findings in α-diversity. Notably, the pathogen Plesiomonas shigelloides was significantly increased in the posterior intestine of IL-17RA1 KO medaka. These findings indicate that signaling via IL-17RA1 is required to maintain a healthy gut microbiota in teleosts and mammals. The involvement of IL-17RA1 in controlling the gut microbiota has been demonstrated, resulting in microbiome dysbiosis in IL-17RA1 KO medaka.
肠免疫系统与肠道微生物群之间的相互关系受到了广泛关注。在哺乳动物中，白细胞介素-17A 和 F（IL-17A/F）是炎症细胞因子，也是肠道微生物群的关键调节剂。然而，在硬骨鱼中，IL-17A/F 控制肠道微生物群的功能尚未得到充分理解。我们试图阐明硬骨鱼 IL-17 信号在控制肠道微生物群中的重要性。我们先前使用 CRISPR-Cas9 系统在日本青鳉（Oryzias latipes）中建立了白细胞介素-17 受体 A（RA）1 的敲除（KO），IL-17A/F 的受体，并使用 16S rRNA 为基础的宏基因组分析在前肠和后肠的肠道节段。与野生型（WT）相比，IL-17RA1 KO 青鳉的前肠观察到的 OTUs 数量明显减少。此外，β多样性分析（加权 UniFrac）显示 IL-17RA1 KO 与 WT 相比，前肠的细菌组成有很大差异，α多样性也有类似的发现。值得注意的是，病原体类志贺邻单胞菌在 IL-17RA1 KO 青鳉的后肠中显著增加。这些发现表明，在硬骨鱼和哺乳动物中，IL-17RA1 信号传导对于维持健康的肠道微生物群是必要的。IL-17RA1 参与控制肠道微生物群，导致 IL-17RA1 KO 青鳉的微生物组失调。
