Li Yang-Yang, Pearson James A, Chao Chen, Peng Jian, Zhang Xiaojun, Zhou Zhiguang, Liu Yu, Wong F Susan, Wen Li
Section of Endocrinology, School of Medicine, Yale University, New Haven, CT, 06519, USA; Department of Endocrinology, The 2nd Hospital of Jilin University, Changchun, Jilin, 130041, China.
Section of Endocrinology, School of Medicine, Yale University, New Haven, CT, 06519, USA.
J Autoimmun. 2017 Aug;82:85-95. doi: 10.1016/j.jaut.2017.05.007. Epub 2017 Jun 4.
Nucleotide-binding oligomerization domain-containing protein 2 (Nod2) is an innate immune receptor. To investigate the role of Nod2 in susceptibility to the autoimmune disease, type 1 diabetes mellitus (T1DM), we generated Nod2 non-obese diabetic (NOD) mice. The Nod2NOD mice had different composition of the gut microbiota compared to Nod2NOD mice and were significantly protected from diabetes, but only when housed separately from Nod2NOD mice. This suggested that T1DM susceptibility in Nod2NOD mice is dependent on the alteration of gut microbiota, which modulated the frequency and function of IgA-secreting B-cells and IL-10 promoting T-regulatory cells. Finally, colonizing germ-free NOD mice with Nod2NOD gut microbiota significantly reduced pro-inflammatory cytokine-secreting immune cells but increased T-regulatory cells. Thus, gut microbiota modulate the immune system and T1D susceptibility. Importantly, our study raises a critical question about the housing mode in the interpretation of the disease phenotype of genetically-modified mouse strains in T1DM studies.
含核苷酸结合寡聚化结构域蛋白2（Nod2）是一种天然免疫受体。为了研究Nod2在自身免疫性疾病1型糖尿病（T1DM）易感性中的作用，我们培育了Nod2非肥胖糖尿病（NOD）小鼠。与野生型NOD小鼠相比，Nod2NOD小鼠的肠道微生物群组成不同，并且显著受到糖尿病的保护，但只有在与野生型NOD小鼠分开饲养时才会如此。这表明野生型NOD小鼠中T1DM易感性取决于肠道微生物群的改变，肠道微生物群改变调节了分泌IgA的B细胞的频率和功能以及促进白细胞介素10的调节性T细胞的功能。最后，用野生型NOD小鼠的肠道微生物群定殖无菌NOD小鼠，显著减少了分泌促炎细胞因子的免疫细胞，但增加了调节性T细胞。因此，肠道微生物群调节免疫系统和T1D易感性。重要的是，我们的研究在T1DM研究中对转基因小鼠品系疾病表型的解释中提出了一个关于饲养模式的关键问题。
