The frequency of Th17 cells in the small intestine exhibits a day-night varidation dependent on circadian clock activity.
The frequency of Th17 cells in the small intestine exhibits a day-night varidation dependent on circadian clock activity.
复制标题
小肠中 Th17 细胞的频率表现出依赖于生物钟活动的昼夜变化。
DOI：
10.1016/j.bbrc.2017.06.038
复制
发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Nakao A
中科院分区：
文献类型：
--
作者：
Thu Le HP;Nakamura Y;Oh-Oka K;Ishimaru K;Nakajima S;Nakao A
产生白细胞介素-17的CD 4 +T辅助细胞（Th 17）是一种关键的免疫谱系，其保护粘膜表面免受细菌和真菌感染。在稳态下，Th 17细胞在小鼠的小肠粘膜中是丰富的。有几种调节小肠中Th 17细胞数量的机制，反映了保持其数量处于正确平衡的重要性。在这里，我们证明了野生型小鼠小肠固有层中Th 17细胞频率存在时间依赖性变化，而在异常光/暗条件下饲养的核心昼夜节律基因Clockor功能丧失突变的小鼠中未观察到这种变化。与此相一致的是，CCL 20（一种调节Th 17细胞向小肠稳态运输的趋化因子）的表达在野生型小鼠的小肠中表现出昼夜节律，而在Clock突变小鼠的小肠中则没有。为了支持这些观察结果，卵清蛋白（OVA）特异性抗体和T细胞反应的小鼠致敏的OVA加霍乱毒素，粘膜Th 17细胞依赖性佐剂的幅度，与每天的变化在小肠中的Th 17细胞的比例。这些结果表明，在小肠中的Th 17细胞的比例表现出昼夜变化与CCL 20的表达，这取决于生物钟活动。这些发现为稳态下小肠中Th 17细胞群的调节提供了新的见解，这可能对粘膜疫苗接种策略具有转化潜力。
Interleukin-17–producing CD4+T helper (Th17) cells are a key immune lineage that protects against bacterial and fungal infections at mucosal surfaces. At steady state, Th17 cells are abundant in the small intestinal mucosa of mice. There are several mechanisms for regulating the population of Th17 cells in the small intestine, reflecting the importance of maintaining their numbers in the correct balance. Here we demonstrate the existence of a time-of-day–dependent variation in the frequency of Th17 cells in the lamina propria of the small intestine in wild-type mice, which was not observed in mice with a loss-of-function mutation of the core circadian geneClockor in mice housed under aberrant light/dark conditions. Consistent with this, expression of CCL20, a chemokine that regulates homeostatic trafficking of Th17 cells to the small intestine, exhibited circadian rhythms in the small intestine of wild-type, but notClock-mutated, mice. In support of these observations, the magnitude of ovalbumin (OVA)-specific antibody and T-cell responses in mice sensitized with OVA plus cholera toxin, a mucosal Th17 cell–dependent adjuvant, was correlated with daily variations in the proportion of Th17 cells in the small intestine. These results suggest that the proportion of Th17 cells in the small intestine exhibits a day–night variation in association with CCL20 expression, which depends on circadian clock activity. The findings provide novel insight into the regulation of the Th17 cell population in the small intestine at steady state, which may have translational potential for mucosal vaccination strategies.