HMGB1 suppress the expression of IL-35 by regulating Naive CD4+T cell differentiation and aggravating Caspase-11-dependent pyroptosis in acute lung injury
HMGB1 suppress the expression of IL-35 by regulating Naive CD4+T cell differentiation and aggravating Caspase-11-dependent pyroptosis in acute lung injury
复制标题
HMGB1通过调节Naâve CD4 T细胞分化并加重急性肺损伤中Caspase-11依赖性细胞焦亡来抑制IL-35的表达
DOI：
10.1016/j.intimp.2020.107295
复制
发表时间：
2021-02-01
影响因子：
5.6
通讯作者：
Xu，Fang
中科院分区：
文献类型：
--
作者：
Xie，Ke;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）是一种严重的炎性肺疾病。它的发育和进展受细胞因子的调节。本研究的目的是确定HMGB1参与Treg细胞和IL-35调控的作用。方法采用盲肠结扎穿刺（CLP）诱导ALI模型，观察HMGB1抑制（甘草酸作为HMGB1抑制剂）后IL-35、Tregs及RAGE、caspase-11表达的变化。培养C57BL/6小鼠脾脏CD4+ naïve T细胞，探讨HMGB1在CD4+ naïve T细胞向treg细胞分化中的作用。结果shmgb1促进CLP小鼠肺损伤和炎症失控。甘草酸预处理后CLP小鼠肺组织HMGB1、NF-κB p65、RAGE、caspase-11表达明显降低。我们发现抑制HMGB1后，CLP小鼠血清和肺中Treg比例和IL-35表达上调。在我们的体外实验中，我们发现重组HMGB1显著抑制CD4+CD25+FOXP3+Tregs从CD4+ naïve T细胞分化的比例。结论抑制HMGB1可提高clp诱导的ALI模型中Treg的比例和IL-35的表达，减轻肺损伤。此外，抑制HMGB1可减少clp诱导的ALI模型肺中caspase-11依赖性焦亡。
ObjectivesAcute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a severe form of inflammatory lung disease. Its development and progression are regulated by cytokines. The purpose of this study was to determine the effects of HMGB1 involved in the regulation of Treg cells and IL-35.MethodsA cecal ligation and puncture (CLP)-induced ALI model was used to investigate the changes in IL-35, Tregs, and the expression of RAGE and caspase-11 after HMGB1 inhibition (glycyrrhizin was used as an inhibitor of HMGB1). CD4+ naïve T cells sorted from C57BL/6 mice spleens were cultured to explore the role of HMGB1 in the differentiation from CD4+ naïve T cells to Tregs.ResultsHMGB1 promoted lung injury and uncontrolled inflammation in the CLP mouse model. HMGB1, NF-κB p65, RAGE, and caspase-11 expression in the lungs of CLP mice decreased significantly after pretreatment with glycyrrhizin. We found that the Treg proportion and IL-35 expression were upregulated in the serum and lung of CLP mice after inhibiting HMGB1. In ourin vitroexperiments, we found that recombinant HMGB1 significantly suppressed the proportion of CD4+CD25+FOXP3+Tregs differentiated from CD4+ naïve T cells.ConclusionsThe inhibition of HMGB1 increased the proportion of Treg and expression of IL-35 and alleviated lung injury in the CLP-induced ALI model. Furthermore, inhibition of HMGB1 reduced caspase-11-dependent pyroptosis in the lungs of the CLP-induced ALI model.