Curcumin regulates the differentiation of naive CD4+T cells and activates IL-10 immune modulation against acute lung injury in mice
Curcumin regulates the differentiation of naive CD4+T cells and activates IL-10 immune modulation against acute lung injury in mice
复制标题
姜黄素调节幼稚 CD4 T 细胞的分化并激活 IL-10 免疫调节对抗小鼠急性肺损伤
DOI：
10.1016/j.biopha.2020.109946
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发表时间：
2020-05-01
影响因子：
7.5
通讯作者：
Xu, Fang
中科院分区：
文献类型：
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作者：
Chai, Yu-sen;Chen, Yan-qing;Xu, Fang
目的：急性肺损伤/急性呼吸窘迫综合征（Acute lung injury/ Acute respiratory distress syndrome, ALI/ARDS）是一种呼吸衰竭，其特征是肺部广泛炎症的快速发作。据报道，姜黄素通过增强调节性T细胞（Tregs）的功能而成为一种抗炎因子。本研究旨在探讨姜黄素在ALI/ARDS中的作用及其对treg细胞分化的影响。方法：采用盲肠结扎穿刺（CLP）诱导的急性肺损伤小鼠模型，探讨姜黄素在ALI/ARDS中的作用。评估肺损伤的严重程度。检测肺组织中IL-17A和MPO的免疫组化。检测血清和支气管肺泡灌洗液（BALF）中treg相关细胞因子水平。检测肺组织核因子κ B （nf - κ B）的表达。免疫荧光法检测肺组织中巨噬细胞。定量脾CD4+CD25+FOXP3+ Tregs，并评价Tregs与初始CD4+ T细胞和STAT5的分化情况。检测IL-10在体外初始CD4 + T细胞分化过程中的表达。结果：姜黄素可减轻CLP小鼠模型肺损伤，抑制炎症反应。姜黄素预处理后CLP小鼠肺组织中IL-17A、mpo生成中性粒细胞和NF-kappa B p65的表达显著降低。我们发现姜黄素可以调节CLP小鼠肺中M1/M2巨噬细胞水平。这可能是通过调节treg的分化和treg衍生的IL-10的产生。treg衍生的IL-10是影响巨噬细胞极化的主要因子。我们发现姜黄素可以增加体内Treg的比例，上调血清IL-10和BALF的表达。在我们的体外实验中，我们发现姜黄素可以促进Treg分化，增加IL-10的产生。结论：姜黄素可通过促进未成熟CD4+ T细胞向CD4+ CD25+ FOXP3+ Tregs细胞分化，降低ALI的严重程度和炎症失控程度。姜黄素促进巨噬细胞从M1向M2转化。姜黄素诱导treg的分化可能是IL-10免疫调节的一个来源。
Objectives: Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is one type of respiratory failure characterized by rapid onset of widespread inflammation in the lungs. Curcumin has been reported to be an anti-inflammatory factor through enhancing the function of regulatory T cells (Tregs). This study aimed to explore the effect of curcumin on the differentiation of Tregs and the role of curcumin in ALI/ARDS.Methods: A cecal ligation and puncture (CLP)-induced acute lung injury mouse model was used to explore the effect of curcumin in ALI/ARDS. The severity of lung injury was evaluated. Immunohistochemistry of IL-17A and MPO in lung tissue was examined. Treg-related cytokine levels in serum and bronchoalveolar lavage fluid (BALF) were tested. The expression of nuclear factor-kappa B (NF-kappa B) in lung tissue was detected. Macrophages in lung tissue were detected by immunofluorescence. Splenic CD4+CD25+FOXP3+ Tregs were quantified, and the differentiation of Tregs from naive CD4 + T cell and STAT5 was evaluated. The expression of IL-10 during naive CD4 + T cell differentiation in vitro was tested.Results: Curcumin alleviated lung injury in the induced CLP mouse model and suppressed inflammation. IL-17A, MPO-producing neutrophils, and NF-kappa B p65 expression in lungs of CLP mice decreased significantly after pretreatment with curcumin. We found curcumin could regulate M1/M2 macrophage levels in lungs of CLP mice. This may have been through regulating the differentiation of Tregs and the production of Treg-derived IL-10. Treg-derived IL-10 is the main factor that could affect macrophage polarization. We found curcumin could increase Treg proportions in vivo and up-regulate IL-10 expression in serum and BALF of CLP mice. In our in vitro experiments, we found curcumin could promote Treg differentiation and increase the production of IL-10.Conclusions: Curcumin can reduce the degree of severity of ALI and uncontrolled inflammation through promoting the differentiation of naive CD4 + T cells to CD4+ CD25+ FOXP3+ Tregs. Curcumin promotes the conversion of macrophages from M1 to M2. The differentiation of Tregs induced by curcumin may be one source of IL-10 immune modulation.