NKT cells promote lung injury by inhibiting lung recruitment of DC cell

ZHU Xue; LIU Shiping; WANG Huijuan; ZHANG Yunlong; PAN Mingliang; ZHANG Zhaocai; SONG Zhenju; WANG Lu; ZHAN Liying

doi:10.14188/j.1671-8852.2024.0509

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NKT cells promote lung injury by inhibiting lung recruitment of DC cell

更新时间：2026-11-05

- NKT cells promote lung injury by inhibiting lung recruitment of DC cell
- Medical Journal of Wuhan University Vol. 46, Issue 2, Pages: 142-146(2025)
- 作者机构：
  
  1.武汉大学人民医院重症医学科湖北武汉 430060
  2.浙江大学医学院附属第二医院重症医学科/浙江省急危重症临床医学研究中心浙江杭州 310009
  3.复旦大学附属中山医院急诊科/复旦大学应急救援与急危重症研究所上海 200032
- 作者简介：
- 基金信息：
- DOI：10.14188/j.1671-8852.2024.0509
  CLC： R34
- Received：07 July 2024，
  
  Published：25 February 2025
- 稿件说明：
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竹雪,刘世平,王慧娟等.NKT细胞缺乏通过促进树突状细胞肺部募集减轻肺损伤[J].武汉大学学报（医学版）,2025,46(02):142-146.

ZHU Xue,LIU Shiping,WANG Huijuan,et al.NKT cells promote lung injury by inhibiting lung recruitment of DC cell[J].Medical Journal of Wuhan University,2025,46(02):142-146.
竹雪,刘世平,王慧娟等.NKT细胞缺乏通过促进树突状细胞肺部募集减轻肺损伤[J].武汉大学学报（医学版）,2025,46(02):142-146. DOI： 10.14188/j.1671-8852.2024.0509.

ZHU Xue,LIU Shiping,WANG Huijuan,et al.NKT cells promote lung injury by inhibiting lung recruitment of DC cell[J].Medical Journal of Wuhan University,2025,46(02):142-146. DOI： 10.14188/j.1671-8852.2024.0509.

摘要

目的

探讨自然杀伤T（NKT）细胞促进急性呼吸窘迫综合征（ARDS）肺损伤的机制。

方法

利用野生型C57BL/6和CD1d基因敲除小鼠（NKT细胞缺乏），采用气管滴注脂多糖（LPS）的方式构建ARDS模型，分为WT⁃Control组、WT⁃ARDS组、CD1d

-/-

⁃Control组和CD1d

-/-

⁃ARDS组。观察肺组织病理损伤；检测肺组织湿干重比、肺泡灌洗液蛋白浓度及中性粒细胞比例、肺组织树突状细胞（DC）比例及炎症因子变化。

结果

与WT⁃ARDS组相比，CD1d

-/-

⁃ARDS组病死率降低，HE染色显示肺组织病理损伤减轻，肺损伤评分减低，肺毛细血管内皮通透性降低（

0.05）；而且缺乏NKT细胞ARDS小鼠肺组织DC细胞比例升高，促炎性细胞因子IL⁃6、TNF⁃α减少，抑炎性细胞因子IL⁃10增多（

0.05）。

结论

NKT细胞通过抑制DC细胞肺部募集加重ARDS肺损伤。

Abstract

Objective

To investigate the mechanism of Natural Killer T (NKT) cells promoting lung injury in acute respiratory distress syndrome （ARDS）.

Methods

In this study

ARDS mouse models were induced in wild⁃type (C57BL/6) and CD1d knockout (KO) mice by intratracheal instillation of lipopolysaccharide (LPS). The mice were divided into four groups: the WT⁃Control

the WT⁃ARDS

the CD1d

-/-

⁃Control

and the CD1d

-/-

⁃ARDS. We observed the pathological changes in lung tissue and measured the wet/dry (W/D) weight ratio of the lung. Protein concentration and neutrophil ratio in bronchoalveolar lavage fluid (BALF)

the proportion of dendritic cells（DCs) and inflammatory factor levels in the lung were also measured.

Results

Compared with those in the WT⁃ARDS group

the mortality

lung injury score and pulmonary capillary permeability all decreased significantly in the CD1d

-/-

⁃ARDS group (

0.05). HE staining showed that the pathological state of the lung tissues improved obviously in CD1d KO mice. Besides

levels of pro⁃inflammatory cytokines (IL⁃6 and TNF⁃α) were decreased and the expression of anti⁃inflammatory cytokine (IL⁃10) was increased (

0.05). The proportion of DCs in lung tissues was increased after CD1d gene KO (

0.05).

Conclusion

NKT cells aggravate ARDS lung injury by inhibiting lung recruitment of DCs.

关键词

Keywords

references

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Kim D M , Seo J W , Kim Y , et al . Eosinophil⁃mediated lung inflammation associated with elevated natural killer T cell response in COVID⁃19 patients [J ] . Korean J Intern Med , 2022 , 37 ( 1 ): 201 ⁃ 209 .

Crosby C M , Kronenberg M . Tissue⁃specific functions of invariant natural killer T cells [J ] . Nat Rev Immunol , 2018 , 18 ( 9 ): 559 ⁃ 574 .

Bourgeois E A , Levescot A , Diem S , et al . A natural protective function of invariant NKT cells in a mouse model of innate⁃cell⁃driven lung inflammation [J ] . Eur J Immunol , 2011 , 41 ( 2 ): 299 ⁃ 305 .

Zhao L , Gao X , Bai H , et al . The important role of dendritic cell (DC) in iNKT⁃mediated modulation of NK cell function in chlamydia pneumoniae lung infection [J ] . Mediators Inflamm , 2019 , 2019 : 4742634 .

Shekhar S , Joyee A G , Gao X , et al . Invariant natural killer T cells promote T cell immunity by modulating the function of lung dendritic cells during chlamydia pneumoniae infection [J ] . J Innate Immun , 2015 , 7 ( 3 ): 260 ⁃ 274 .

Shekhar S , Joyee A G , Gao X , et al . Invariant NKT cells preferentially modulate the function of CD8 alpha + dendritic cell subset in inducing type 1 immunity against infection [J ] . J Immunol , 2010 , 184 ( 4 ): 2095 ⁃ 2106 .

Wang L , Wang T , Li H , et al . Receptor interacting protein 3⁃mediated necroptosis promotes lipopolysaccharide⁃induced inflammation and acute respiratory distress syndrome in mice [J ] . PLoS One , 2016 , 11 ( 5 ): e0155723 .

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