Inhibition of Type 1 Diabetes Correlated to a Lactobacillus johnsonii N6.2-Mediated Th17 Bias
Inhibition of Type 1 Diabetes Correlated to a Lactobacillus johnsonii N6.2-Mediated Th17 Bias
复制标题
DOI：
10.4049/jimmunol.1001864
复制
发表时间：
2011-03-15
影响因子：
4.4
通讯作者：
Larkin, Joseph, III
中科院分区：
文献类型：
--
作者：
Lau, Kenneth;Benitez, Patrick;Larkin, Joseph, III
虽然已知肠道菌群有助于免疫系统功能和体内平衡，但它们在自身免疫性疾病1型糖尿病(T1D)进展中的作用尚不清楚。从T1D的经典模型生物繁育大鼠分离的粪便样本比较表明，在自发生物繁育糖尿病易感(BBDP)和生物繁育糖尿病抵抗动物中存在不同的细菌种群。我们先前已经证明，口服从生物育种糖尿病耐药的BBDP啮齿动物中转移的约翰乳杆菌N6.2(LjN6.2)可以赋予T1D对BBDP啮齿动物的抗性，而鲁氏乳杆菌菌株Td1则不能。在这项研究中，我们证明了喂食LjN6.2的BBDP啮齿动物的糖尿病抵抗与肠系膜淋巴结内Th17细胞的偏向有关。在非肠道引流的腋窝淋巴结中未观察到Th17偏向，提示Th17偏向是由于免疫系统与LjN6.2在肠系膜淋巴结内的相互作用所致。在服用LjN6.2的糖尿病抵抗大鼠的脾中观察到了LjN6.2与免疫系统的相互作用，因为与对照组或喂饲LjN6.2菌株Td1的大鼠相比，它们也具有Th17偏向。用C57BL/6小鼠进行的体外实验表明，在TCR刺激下，LjN6.2直接介导了淋巴细胞对Th17的分化，这需要APC。最后，我们证明，用LjN6.2冲击的树突状细胞足垫接种NOD小鼠足以在体内介导Th17偏向。综上所述，这些数据提出了一个有趣的范式，即肠道菌群介导的Th17分化可以绕过T1D诱导。免疫学杂志，2011,186：3538-3546。
Although it is known that resident gut flora contribute to immune system function and homeostasis, their role in the progression of the autoimmune disease type 1 diabetes (T1D) is poorly understood. Comparison of stool samples isolated from Bio-Breeding rats, a classic model of T1D, shows that distinct bacterial populations reside in spontaneous Bio-Breeding diabetes-prone (BBDP) and Bio-Breeding diabetes-resistant animals. We have previously shown that the oral transfer of Lactobacillus johnsonii strain N6.2 (LjN6.2) from Bio-Breeding diabetes-resistant to BBDP rodents conferred T1D resistance to BBDP rodents, whereas Lactobacillus reuteri strain TD1 did not. In this study, we show that diabetes resistance in LjN6.2-fed BBDP rodents was correlated to a Th17 cell bias within the mesenteric lymph nodes. The Th17 bias was not observed in the non-gut-draining axillary lymph nodes, suggesting that the Th17 bias was because of immune system interactions with LjN6.2 within the mesenteric lymph node. LjN6.2 interactions with the immune system were observed in the spleens of diabetes-resistant, LjN6.2-fed BBDP rats, as they also possessed a Th17 bias in comparison with control or Lactobacillus reuteri strain TD1-fed rats. Using C57BL/6 mouse in vitro assays, we show that LjN6.2 directly mediated enhanced Th17 differentiation of lymphocytes in the presence of TCR stimulation, which required APCs. Finally, we show that footpad vaccination of NOD mice with LjN6.2-pulsed dendritic cells was sufficient to mediate a Th17 bias in vivo. Together, these data suggest an interesting paradigm whereby T1D induction can be circumvented by gut flora-mediated Th17 differentiation. The Journal of Immunology, 2011, 186: 3538-3546.