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Abstract：
BACKGROUND: Recent research has focused on the role of immune cells and immune responses in the pathogenesis of bronchopulmonary dysplasia (BPD), but the exact mechanisms have not yet been elucidated. Previously, the key roles of type 2 innate lymphoid cells (ILC2) in the lung immune network of BPD were explored. Here, we investigated the role Th17 cell response in hyperoxia-induced lung injury of BPD, as well as the relationship between ILC2 and Th17 cell response.
METHODS: A hyperoxia-induced BPD mouse model was constructed and the pathologic changes of lung tissues were evaluated by Hematoxylin-Eosin staining. Flow cytometry analysis was conducted to determine the levels of Th17 cell, ILC2 and IL-6+ILC2. The expression levels of IL-6, IL-17 A, IL-17 F, and IL-22 in the blood serum and lung tissues of BPD mice were measured by ELISA. To further confirm the relationship between ILC2 and Th17 cell differentiation, ILC2 depletion was performed in BPD mice. Furthermore, we used immunomagnetic beads to enrich ILC2 and then flow-sorted mouse lung CD45+Lin-CD90.2+Sca-1+ILC2. The sorted ILC2s were injected into BPD mice via tail vein. Following ILC2 adoptive transfusion, the changes of Th17 cell response and lung injury were detected in BPD mice.
RESULTS: The expression levels of Th17 cells and Th17 cell-related cytokines, including IL-17 A, IL-17 F, and IL-22, were significantly increased in BPD mice. Concurrently, there was a significant increase in the amount of ILC2 and IL-6+ILC2 during hyperoxia-induced lung injury, which was consistent with the trend for Th17 cell response. Compared to the control BPD group, ILC2 depletion was found to partially abolish the Th17 cell response and had protective effects against lung injury after hyperoxia. Furthermore, the adoptive transfer of ILC2 enhanced the Th17 cell response and aggravated lung injury in BPD mice.
CONCLUSIONS: This study found that ILC2 regulates hyperoxia-induced lung injury by targeting the Th17 cell response in BPD, which shows a novel strategy for BPD immunotherapy.
METHODS: A hyperoxia-induced BPD mouse model was constructed and the pathologic changes of lung tissues were evaluated by Hematoxylin-Eosin staining. Flow cytometry analysis was conducted to determine the levels of Th17 cell, ILC2 and IL-6+ILC2. The expression levels of IL-6, IL-17 A, IL-17 F, and IL-22 in the blood serum and lung tissues of BPD mice were measured by ELISA. To further confirm the relationship between ILC2 and Th17 cell differentiation, ILC2 depletion was performed in BPD mice. Furthermore, we used immunomagnetic beads to enrich ILC2 and then flow-sorted mouse lung CD45+Lin-CD90.2+Sca-1+ILC2. The sorted ILC2s were injected into BPD mice via tail vein. Following ILC2 adoptive transfusion, the changes of Th17 cell response and lung injury were detected in BPD mice.
RESULTS: The expression levels of Th17 cells and Th17 cell-related cytokines, including IL-17 A, IL-17 F, and IL-22, were significantly increased in BPD mice. Concurrently, there was a significant increase in the amount of ILC2 and IL-6+ILC2 during hyperoxia-induced lung injury, which was consistent with the trend for Th17 cell response. Compared to the control BPD group, ILC2 depletion was found to partially abolish the Th17 cell response and had protective effects against lung injury after hyperoxia. Furthermore, the adoptive transfer of ILC2 enhanced the Th17 cell response and aggravated lung injury in BPD mice.
CONCLUSIONS: This study found that ILC2 regulates hyperoxia-induced lung injury by targeting the Th17 cell response in BPD, which shows a novel strategy for BPD immunotherapy.
摘要：
背景：最近的研究集中在免疫细胞和免疫反应在支气管肺发育不良（BPD）发病机理中的作用，但确切的机制尚未阐明。以前,探讨了2型固有淋巴细胞（ILC2）在BPD肺免疫网络中的关键作用。这里,我们研究了Th17细胞反应在高氧诱导的BPD肺损伤中的作用，以及ILC2与Th17细胞反应之间的关系。
方法：建立高氧诱导的BPD小鼠模型，并通过苏木精-伊红染色观察肺组织的病理变化。进行流式细胞术分析以确定Th17细胞的水平，ILC2和IL-6+ILC2。IL-6，IL-17A的表达水平，IL-17F,ELISA法测定BPD小鼠血清和肺组织中IL-22的含量。为了进一步证实ILC2与Th17细胞分化的关系，在BPD小鼠中进行ILC2消除。此外，我们使用免疫磁珠富集ILC2，然后流式分选小鼠肺CD45+Lin-CD90.2+Sca-1+ILC2。通过尾静脉将分选的ILC2s注射到BPD小鼠中。在ILC2过继输血后，检测BPD小鼠Th17细胞反应和肺损伤的变化。
结果：Th17细胞和Th17细胞相关细胞因子的表达水平，包括IL-17A,IL-17F,和IL-22在BPD小鼠中显著升高。同时,在高氧诱导的肺损伤期间，ILC2和IL-6+ILC2的量显著增加，这与Th17细胞反应的趋势一致。与对照BPD组相比，发现ILC2耗竭部分消除了Th17细胞反应，并对高氧后的肺损伤具有保护作用。此外，ILC2的过继转移增强了BPD小鼠的Th17细胞反应并加重了肺损伤。
结论：这项研究发现，ILC2通过靶向BPD中的Th17细胞反应来调节高氧诱导的肺损伤，这显示了BPD免疫治疗的新策略。
方法：建立高氧诱导的BPD小鼠模型，并通过苏木精-伊红染色观察肺组织的病理变化。进行流式细胞术分析以确定Th17细胞的水平，ILC2和IL-6+ILC2。IL-6，IL-17A的表达水平，IL-17F,ELISA法测定BPD小鼠血清和肺组织中IL-22的含量。为了进一步证实ILC2与Th17细胞分化的关系，在BPD小鼠中进行ILC2消除。此外，我们使用免疫磁珠富集ILC2，然后流式分选小鼠肺CD45+Lin-CD90.2+Sca-1+ILC2。通过尾静脉将分选的ILC2s注射到BPD小鼠中。在ILC2过继输血后，检测BPD小鼠Th17细胞反应和肺损伤的变化。
结果：Th17细胞和Th17细胞相关细胞因子的表达水平，包括IL-17A,IL-17F,和IL-22在BPD小鼠中显著升高。同时,在高氧诱导的肺损伤期间，ILC2和IL-6+ILC2的量显著增加，这与Th17细胞反应的趋势一致。与对照BPD组相比，发现ILC2耗竭部分消除了Th17细胞反应，并对高氧后的肺损伤具有保护作用。此外，ILC2的过继转移增强了BPD小鼠的Th17细胞反应并加重了肺损伤。
结论：这项研究发现，ILC2通过靶向BPD中的Th17细胞反应来调节高氧诱导的肺损伤，这显示了BPD免疫治疗的新策略。
