Evidence map›Paper›PMID 38987753›Full record

ArticleRespiratory research2024

Necroptosis plays a role in TL1A-induced airway inflammation and barrier damage in asthma.

Xiaofei Liu, Jintao Zhang, Dong Zhang, Yun Pan, Rong Zeng, Changjuan Xu, Shuochuan Shi, Jiawei Xu, Qian Qi, Xueli Dong and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Respiratory research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed.

  1. Review
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  9. Juglans regiaJournal of tropical medicine · 2025
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Xiaofei LiuDepartment of Respiratory, Shandong Institute of Respiratory Diseases, The First Affiliated Hospital of Shandong First Medical University, Jinan, 250014, China.
Jintao ZhangDepartment of Respiratory, Shandong Institute of Respiratory Diseases, The First Affiliated Hospital of Shandong First Medical University, Jinan, 250014, China.
Dong ZhangDepartment of Respiratory, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China.
Yun PanDepartment of Respiratory, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China.
Rong ZengDepartment of Respiratory, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China.
Changjuan XuDepartment of Respiratory, Shandong Institute of Respiratory Diseases, The First Affiliated Hospital of Shandong First Medical University, Jinan, 250014, China.
Shuochuan ShiDepartment of Respiratory, Shandong Institute of Respiratory Diseases, The First Affiliated Hospital of Shandong First Medical University, Jinan, 250014, China.
Jiawei XuDepartment of Respiratory, Shandong Institute of Respiratory Diseases, The First Affiliated Hospital of Shandong First Medical University, Jinan, 250014, China.
Qian QiDepartment of Respiratory, Shandong Institute of Respiratory Diseases, The First Affiliated Hospital of Shandong First Medical University, Jinan, 250014, China.
Xueli DongDepartment of Respiratory, Shandong Institute of Respiratory Diseases, The First Affiliated Hospital of Shandong First Medical University, Jinan, 250014, China.
Junfei WangDepartment of Respiratory and Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, China.
Tian LiuDepartment of Respiratory and Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, China.
Liang DongDepartment of Respiratory, Shandong Institute of Respiratory Diseases, The First Affiliated Hospital of Shandong First Medical University, Jinan, 250014, China. dl5506@126.com.

Funding

the Jinan Clinical Medicine Research Program for Respiratory Disease 202132002the Key Research and Development Program of Shandong Province 2021SFGC0504the National Natural Science Foundation of China 82270032the Shandong Provincial Natural Science Foundation ZR2021LSW015
6 · The paper itself

Abstract

backgroundAirway epithelial cell (AEC) necroptosis contributes to airway allergic inflammation and asthma exacerbation. Targeting the tumor necrosis factor-like ligand 1 A (TL1A)/death receptor 3 (DR3) axis has a therapeutic effect on asthmatic airway inflammation. The role of TL1A in mediating necroptosis of AECs challenged with ovalbumin (OVA) and its contribution to airway inflammation remains unclear.

methodsWe evaluated the expression of the receptor-interacting serine/threonine-protein kinase 3(RIPK3) and the mixed lineage kinase domain-like protein (MLKL) in human serum and lung, and histologically verified the level of MLKL phosphorylation in lung tissue from asthmatics and OVA-induced mice. Next, using MLKL knockout mice and the RIPK3 inhibitor GSK872, we investigated the effects of TL1A on airway inflammation and airway barrier function through the activation of necroptosis in experimental asthma.

resultsHigh expression of necroptosis marker proteins was observed in the serum of asthmatics, and necroptosis was activated in the airway epithelium of both asthmatics and OVA-induced mice. Blocking necroptosis through MLKL knockout or RIPK3 inhibition effectively attenuated parabronchial inflammation, mucus hypersecretion, and airway collagen fiber accumulation, while also suppressing type 2 inflammatory factors secretion. In addition, TL1A/ DR3 was shown to act as a death trigger for necroptosis in the absence of caspases by silencing or overexpressing TL1A in HBE cells. Furthermore, the recombinant TL1A protein was found to induce necroptosis in vivo, and knockout of MLKL partially reversed the pathological changes induced by TL1A. The necroptosis induced by TL1A disrupted the airway barrier function by decreasing the expression of tight junction proteins zonula occludens-1 (ZO-1) and occludin, possibly through the activation of the NF-κB signaling pathway.

conclusionsTL1A-induced airway epithelial necroptosis plays a significant role in promoting airway inflammation and barrier dysfunction in asthma. Inhibition of the TL1A-induced necroptosis pathway could be a promising therapeutic strategy.

Indexed as

AsthmaMice, KnockoutNecroptosisTumor Necrosis Factor Ligand Superfamily Member 15AnimalsFemaleHumansInflammationMaleMiceMice, Inbred C57BLOvalbuminProtein KinasesReceptor-Interacting Protein Serine-Threonine KinasesMLKL protein, mouseOvalbuminProtein KinasesReceptor-Interacting Protein Serine-Threonine KinasesRIPK3 protein, humanRipk3 protein, mouseTNFSF15 protein, humanTnfsf15 protein, mouseTumor Necrosis Factor Ligand Superfamily Member 15Airway inflammationMLKLNecroptosisNF-κBTight junctionTL1A

Identifiers

PMID38987753
PMCPMC11238433

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