IL-33 Deficiency Attenuates Lung Inflammation by Inducing Th17 Response and Impacting the Th17/Treg Balance in LPS-Induced ARDS Mice via Dendritic Cells

作者全名："Cheng, Li; Jiao, Yang; Jiang, Wei; Zhang, Xin; Zhang, Liping; Jia, Gongwei"

作者地址："[Cheng, Li] Chongqing Med Univ, Dept Hlth Management Ctr, Affiliated Hosp 2, 76 Linjiang Rd, Chongqing 400010, Peoples R China; [Jiao, Yang] Chongqing Med Univ, Dept Resp, Affiliated Hosp 2, 76 Linjiang Rd, Chongqing 400010, Peoples R China; [Jiang, Wei; Zhang, Xin; Jia, Gongwei] Chongqing Med Univ, Dept Rehabil, Affiliated Hosp 2, 76 Linjiang Rd, Chongqing 400010, Peoples R China; [Zhang, Liping] Hubei Coll Chinese Med, Dept Rehabil, 87 Xueyuan Rd, Jingzhou 434020, Hubei, Peoples R China"

通信作者："Jia, GW (通讯作者)，Chongqing Med Univ, Dept Rehabil, Affiliated Hosp 2, 76 Linjiang Rd, Chongqing 400010, Peoples R China."

来源：JOURNAL OF IMMUNOLOGY RESEARCH

ESI学科分类：IMMUNOLOGY

WOS号：WOS:000903627600001

JCR分区：Q3

影响因子：4.1

年份：2022

卷号：2022

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："Objectives. The characteristic pathophysiological feature of acute respiratory distress syndrome (ARDS) is a dysregulated inflammatory response. T helper 17 (Th17) cells in the lung are inflammatory cells that contribute to pulmonary inflammatory cascades. In addition, Th17/regulatory T cells (Treg cells) also play an important role in the inflammatory process. Dendritic cells (DCs) can regulate the differentiation of CD4+ T cells, including Th17 and Treg cells. Recent evidence revealed that interleukin-33 (IL-33) signaling could activate and mature DCs. Therefore, the aim of this study was to investigate the effects of IL-33 on inflammation and immunoregulation by inducing the Th17 response and influencing the Th17/Treg balance in LPS-induced ARDS. Methods. IL-33 gene knockout mice and the administration of recombinant mouse IL-33 (rmIL-33) were used to investigate the role of IL-33 and the underlying mechanisms in an LPS-induced ARDS model. Hematoxylin and eosin (H&E) staining, wet/dry (W/D) weight ratios, cell counts, and the levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), interleukin-17 (IL-17), and interleukin-10 (IL-10) in bronchoalveolar lavage fluid (BALF) were investigated. The levels of IL-33, orphan nuclear receptor gamma t (ROR gamma t), and forkhead transcription factor protein 3 (FOXP3) protein in lung tissue were evaluated by Western blotting. The mRNA expression levels of IL-33 and ROR gamma t were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Th17 and Treg cell frequencies were determined by flow cytometry. The levels of IL-6 in the supernatant in a dendritic cell culture system were examined by ELISA. Results. Increased expression of IL-33 was observed in mice with LPS-induced ARDS. IL-33 deficiency significantly inhibited inflammation and attenuated LPS-induced ARDS, whereas pretreatment with rmIL-33 aggravated pulmonary inflammatory response. Furthermore, depletion of IL-33 inhibited Th17 cells, significantly decreased ROR gamma t mRNA and protein expression and IL-17 levels in BALF, and led to less differentiation of T cells into Th17 cells than Treg cells. Moreover, IL-33(-/-) DCs secreted less IL-6 and IL-23 than normal control DCs. Conclusion. IL-33 deficiency alleviated lung injury in the LPS-induced ARDS model, which was closely related to suppressing Th17 responses and regulating the Th17/Treg balance. The expansion of Th17 cells and imbalance in Th17/Treg cells may be associated with IL-6 and IL-23 secreted from IL-33-activated DCs."

基金机构：National Nature Science Foundation of China [81900079]; Natural Science Foundation of Chongqing [cstc2020jcyj-msxmX0238]; Chongqing Medical Scientific Research Project (Joint Project of Chongqing Health Commission and Science and Technology Bureau) [2020MSXM036]; Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University

基金资助正文："This work was supported by the National Nature Science Foundation of China (grant 81900079), the Natural Science Foundation of Chongqing (grant cstc2020jcyj-msxmX0238), the Chongqing Medical Scientific Research Project (Joint Project of Chongqing Health Commission and Science and Technology Bureau) (grant 2020MSXM036), and the Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University."