PMID- 36570798 OWN - NLM STAT- MEDLINE DCOM- 20221227 LR - 20230103 IS - 2314-7156 (Electronic) IS - 2314-8861 (Print) IS - 2314-7156 (Linking) VI - 2022 DP - 2022 TI - IL-33 Deficiency Attenuates Lung Inflammation by Inducing Th17 Response and Impacting the Th17/Treg Balance in LPS-Induced ARDS Mice via Dendritic Cells. PG - 9543083 LID - 10.1155/2022/9543083 [doi] LID - 9543083 AB - 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-1beta (IL-1beta), 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 (RORgammat), and forkhead transcription factor protein 3 (FOXP3) protein in lung tissue were evaluated by Western blotting. The mRNA expression levels of IL-33 and RORgammat 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 RORgammat 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. CI - Copyright (c) 2022 Li Cheng et al. FAU - Cheng, Li AU - Cheng L AUID- ORCID: 0000-0001-9567-8903 AD - Department of Health Management Center, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing 400010, China. FAU - Jiao, Yang AU - Jiao Y AUID- ORCID: 0000-0003-0090-2349 AD - Department of Respiratory, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing 400010, China. FAU - Jiang, Wei AU - Jiang W AUID- ORCID: 0000-0002-0744-7724 AD - Department of Rehabilitation, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing 400010, China. FAU - Zhang, Xin AU - Zhang X AUID- ORCID: 0000-0002-2557-9317 AD - Department of Rehabilitation, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing 400010, China. FAU - Zhang, Liping AU - Zhang L AUID- ORCID: 0000-0003-1240-331X AD - Department of Rehabilitation, Hubei College of Chinese Medicine, 87 Xueyuan Road, Jingzhou, Hubei Province 434020, China. FAU - Jia, Gongwei AU - Jia G AUID- ORCID: 0000-0002-9151-5207 AD - Department of Rehabilitation, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing 400010, China. LA - eng PT - Journal Article DEP - 20221216 PL - Egypt TA - J Immunol Res JT - Journal of immunology research JID - 101627166 RN - 0 (Interleukin-17) RN - 0 (Interleukin-33) RN - 0 (Lipopolysaccharides) RN - 0 (Interleukin-6) RN - 0 (Nuclear Receptor Subfamily 1, Group F, Member 3) RN - 0 (Immunologic Factors) RN - 0 (RNA, Messenger) RN - 0 (Interleukin-23) SB - IM MH - Mice MH - Animals MH - T-Lymphocytes, Regulatory MH - Interleukin-17 MH - Interleukin-33 MH - Lipopolysaccharides/pharmacology MH - Interleukin-6 MH - Nuclear Receptor Subfamily 1, Group F, Member 3/genetics MH - *Pneumonia MH - Inflammation MH - Immunologic Factors/pharmacology MH - *Respiratory Distress Syndrome MH - RNA, Messenger MH - Dendritic Cells MH - Interleukin-23/pharmacology MH - Th17 Cells PMC - PMC9788894 COIS- The authors state no conflicts of interest in this work. EDAT- 2022/12/27 06:00 MHDA- 2022/12/28 06:00 PMCR- 2022/12/16 CRDT- 2022/12/26 04:42 PHST- 2022/09/13 00:00 [received] PHST- 2022/11/25 00:00 [revised] PHST- 2022/11/26 00:00 [accepted] PHST- 2022/12/26 04:42 [entrez] PHST- 2022/12/27 06:00 [pubmed] PHST- 2022/12/28 06:00 [medline] PHST- 2022/12/16 00:00 [pmc-release] AID - 10.1155/2022/9543083 [doi] PST - epublish SO - J Immunol Res. 2022 Dec 16;2022:9543083. doi: 10.1155/2022/9543083. eCollection 2022.