Interleukin-27 exacerbates acute lung injury by promoting T helper type 1 differentiation via the JAK2/STAT1 pathway

Wang Yuanyang; Xu Fang; Qi Haifeng

doi:10.13406/j.cnki.cyxb.003682

您当前的位置：

首页 >

文章列表页 >

Interleukin-27 exacerbates acute lung injury by promoting T helper type 1 differentiation via the JAK2/STAT1 pathway

Basic research | 更新时间：2025-10-23

- Interleukin-27 exacerbates acute lung injury by promoting T helper type 1 differentiation via the JAK2/STAT1 pathway
- Journal of Chongqing Medical University Vol. 49, Issue 12, Pages: 1572-1576(2024)
- 作者机构：
  
  1.重庆医科大学附属第一医院重症医学科，重庆 400016
  2.重庆医科大学附属妇女儿童医院重症医学科，重庆 401147
- 作者简介：
- 基金信息：
- DOI：10.13406/j.cnki.cyxb.003682
  CLC： R473.72
- Received：05 November 2024，
  
  Revised：2024-11-22，
  
  Accepted：25 November 2024，
  
  Published：28 December 2024
- 稿件说明：
移动端阅览
王远扬,徐昉,祁海峰.IL-27通过JAK2/STAT1通路促进Th1细胞分化加重急性肺损伤[J].重庆医科大学学报,2024,49(12):1572-1576.

Wang Yuanyang,Xu Fang,Qi Haifeng.Interleukin-27 exacerbates acute lung injury by promoting T helper type 1 differentiation via the JAK2/STAT1 pathway[J].Journal of Chongqing Medical University,2024,49(12):1572-1576.
王远扬,徐昉,祁海峰.IL-27通过JAK2/STAT1通路促进Th1细胞分化加重急性肺损伤[J].重庆医科大学学报,2024,49(12):1572-1576. DOI： 10.13406/j.cnki.cyxb.003682.

Wang Yuanyang,Xu Fang,Qi Haifeng.Interleukin-27 exacerbates acute lung injury by promoting T helper type 1 differentiation via the JAK2/STAT1 pathway[J].Journal of Chongqing Medical University,2024,49(12):1572-1576. DOI： 10.13406/j.cnki.cyxb.003682.

摘要

目的

研究白细胞介素27（interleukin-27，IL-27）对辅助性T细胞1（helper T cell 1，Th1）分化及急性肺损伤的影响与作用机制。

方法

通过盲肠结扎穿刺（cecal ligation and puncture，CLP）构建脓毒症急性肺损伤小鼠模型，苏木精-伊红（hematoxylin-eosin staining，HE）染色评估肺组织病理损伤。采用Western Blot、RT-qPCR检测JAK/STAT通路表达与激活以及T盒转录因子21（T-box transcription factor 21，T-bet）蛋白的表达。

结果

IL-27加重脓毒症小鼠肺损伤。细胞实验表明IL-27显著激活JAK2/STAT1通路磷酸化，上调T-bet蛋白（

0.01）和mRNA水平（

0.05）。抑制STAT1磷酸化后，T-bet表达显著下调（

0.01）。

结论

IL-27通过JAK2/STAT1通路促进Th1分化，加重脓毒症小鼠急性肺损伤。

Abstract

Objective

To investigate the effect and mechanism of interleukin-27（IL-27） on the differentiation of T helper type 1 （Th1） cells and acute lung injury.

Methods

The method of cecal ligation and puncture was used to establish a mouse model of sepsis with acute lung injury，and hematoxylin-eosin staining was used to assess the histopathological damage of the lungs. Western blot and RT-qPCR were used to measure the expression and activation of the JAK/STAT pathway and the protein and mRNA expression levels of T-box transcription factor 21（T-bet）.

Results

IL-27 exacerbated lung injury in mice with sepsis. Cell experiments showed that IL-27 significantly activated the phosphorylation of the JAK2/STAT1 pathway and upregulated the protein and mRNA expression levels of T-bet（

0.01，

0.05）. The expression of T-bet was significantly downregulated after inhibition of STAT1 phosphorylation（

0.01）.

Conclusion

IL-27 promotes Th1 differentiation via the JAK2/STAT1 pathway，thereby exacerbating acute lung injury in mice with sepsis.

关键词

Keywords

references

Ashbaugh DG ， Bigelow DB ， Petty TL ， et al . Acute respiratory distress in adults [J ] . Lancet ， 1967 ， 2 （ 7511 ）： 319 - 323 .

Bellani G ， Laffey JG ， Pham T ， et al . Epidemiology，patterns of care，and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries [J ] . JAMA ， 2016 ， 315 （ 8 ）： 788 - 800 .

Medford ARL ， Millar AB . Vascular endothelial growth factor （VEGF） in acute lung injury（ALI） and acute respiratory distress syndrome（ARDS）：paradox or paradigm? [J ] . Thorax ， 2006 ， 61 （ 7 ）： 621 - 626 .

Perl M ， Lomas-Neira J ， Venet F ， et al . Pathogenesis of indirect （secondary） acute lung injury [J ] . Expert Rev Respir Med ， 2011 ， 5 （ 1 ）： 115 - 126 .

Pflanz S ， Timans JC ， Cheung J ， et al . IL-27，a heterodimeric cytokine composed of EBI 3 and p28 protein，induces proliferation of naive CD4 + T cells [J ] . Immunity ， 2002 ， 16 （ 6 ）： 779 - 790 .

Yoshimura T ， Takeda A ， Hamano S ， et al . Two -sided roles of IL-27：induction of Th1 differentiation on naive CD4 + T cells versus suppression of proinflammatory cytokine production including IL-23-induced IL-17 on activated CD4 + T cells partially through STAT3-dependent mechanism [J ] . J Immunol ， 2006 ， 177 （ 8 ）： 5377 - 5385 .

Hunter CA ， Villarino A ， Artis D ， et al . The role of IL-27 in the development of T-cell responses during parasitic infections [J ] . Immunol Rev ， 2004 ， 202 ： 106 - 114 .

Chen Q ， Ghilardi N ， Wang H ， et al . Development of Th1-type immune responses requires the type I cytokine receptor TCCR [J ] . Nature ， 2000 ， 407 （ 6806 ）： 916 - 920 .

Mikawa K ， Nishina K ， Takao Y ， et al . ONO-1714，a nitric oxide synthase inhibitor，attenuates endotoxin-induced acute lung injury in rabbits [J ] . Anesth Analg ， 2003 ， 97 （ 6 ）： 1751 - 1755 .

Bos LDJ ， Ware LB . Acute respiratory distress syndrome：causes，pathophysiology，and phenotypes [J ] . Lancet ， 2022 ， 400 （ 10358 ）： 1145 - 1156 .

van Rijt LS ， Jung S ， Kleinjan A ， et al . In vivo depletion of lung CD11c+ dendritic cells during allergen challenge abrogates the characteristic features of asthma [J ] . J Exp Med ， 2005 ， 201 （ 6 ）： 981 - 991 .

Vermaelen K ， Pauwels R . Pulmonary dendritic cells [J ] . Am J Respir Crit Care Med ， 2005 ， 172 （ 5 ）： 530 - 551 .

Novak N ， Bieber T . 2. Dendritic cells as regulators of immunity and tolerance [J ] . J Allergy Clin Immunol ， 2008 ， 121 （ 2 ）： S370 - S374 .

Morris PE ， Glass J ， Cross R ， et al . Role of T-lymphocytes in the resolution of endotoxin-induced lung injury [J ] . Inflammation ， 1997 ， 21 （ 3 ）： 269 - 278 .

Nakajima T ， Suarez CJ ， Lin KW ， et al . T cell pathways involving CTLA4 contribute to a model of acute lung injury [J ] . J Immunol ， 2010 ， 184 （ 10 ）： 5835 - 5841 .

Tait Wojno ED ， Hunter CA ， Stumhofer JS . The immunobiology of the interleukin-12 family：room for discovery [J ] . Immunity ， 2019 ， 50 （ 4 ）： 851 - 870 .

Awasthi A ， Carrier Y ， Peron JPS ， et al . A dominant function for interleukin 27 in generating interleukin 10-producing anti-inflammatory T cells [J ] . Nat Immunol ， 2007 ， 8 （ 12 ）： 1380 - 1389 .

Pot C ， Apetoh L ， Awasthi A ， et al . Induction of regulatory Tr1 cells and inhibition of T（H） 17 cells by IL-27 [J ] . Semin Immunol ， 2011 ， 23 （ 6 ）： 438 - 445 .

Zhang HY ， Madi A ， Yosef N ， et al . An IL-27-driven transcriptional network identifies regulators of IL-10 expression across T helper cell subsets [J ] . Cell Rep ， 2020 ， 33 （ 8 ）： 108433 .

Xu F ， Liu Q ， Lin SH ， et al . IL-27 is elevated in acute lung injury and mediates inflammation [J ] . J Clin Immunol ， 2013 ， 33 （ 7 ）： 1257 - 1268 .

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Effect of baicalin on alveolar fluid clearance in rats with acute lung injury

Research progress of autophagy in lung inflammatory diseases

Study of pulmonary surfactant and surfactant protein in rats with LPS-induced acute lung injury

Related Author

Luo Xianqin

Liu Chuanxin

Zhou Keyun

Xia Lian

Linghu Li

Yang Yan

Luo Chen

Lin Shihui

Related Institution

College of Traditional Chinese Medicine，Chongqing Medical University

Department of Critical Care Medicine,People’s Hospital of Changshou Chongqing

Department of Emergency and Critical Care Medicine,The First Affiliated Hospital of Chongqing Medical University

Department of Respiratory Medicine，The Second Affiliated Hospital of Chongqing Medical University

Department of Respiratory Medicine，Traditional Chinese Medical Hospital of Jiangbei District

⁰