Evidence map›Paper›PMID 40715082›Full record

ArticleCell death & disease2025

Ferroptosis mediated by the IDO1/Kyn/AhR pathway triggers acute thymic involution in sepsis.

Zimei Cheng, Kexin Wang, Yixue Wang, Tingyan Liu, Jingjing Li, Yaodong Wang, Weiming Chen, Reyihangu Awuti, Hetian Zhou, Wenjia Tong and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death & disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
  5. 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

17 authors.

Zimei Cheng *Department of Emergency and Critical Care Medicine, Children's Hospital of Fudan University, Shanghai Institute of Infectious Disease and Biosecurity, and Institutes of Biomedical Sciences Fudan University, 200032, Shanghai, China.ORCID http://orcid.org/0000-0002-3994-8339
Kexin Wang *Department of Emergency and Critical Care Medicine, Children's Hospital of Fudan University, Shanghai Institute of Infectious Disease and Biosecurity, and Institutes of Biomedical Sciences Fudan University, 200032, Shanghai, China.
Yixue Wang *Department of Emergency and Critical Care Medicine, Children's Hospital of Fudan University, Shanghai Institute of Infectious Disease and Biosecurity, and Institutes of Biomedical Sciences Fudan University, 200032, Shanghai, China.
Tingyan LiuDepartment of Emergency and Critical Care Medicine, Children's Hospital of Fudan University, Shanghai Institute of Infectious Disease and Biosecurity, and Institutes of Biomedical Sciences Fudan University, 200032, Shanghai, China.
Jingjing LiDepartment of Emergency and Critical Care Medicine, Children's Hospital of Fudan University, Shanghai Institute of Infectious Disease and Biosecurity, and Institutes of Biomedical Sciences Fudan University, 200032, Shanghai, China.
Yaodong WangDepartment of Emergency and Critical Care Medicine, Children's Hospital of Fudan University, Shanghai Institute of Infectious Disease and Biosecurity, and Institutes of Biomedical Sciences Fudan University, 200032, Shanghai, China.
Weiming ChenDepartment of Emergency and Critical Care Medicine, Children's Hospital of Fudan University, Shanghai Institute of Infectious Disease and Biosecurity, and Institutes of Biomedical Sciences Fudan University, 200032, Shanghai, China.
Reyihangu AwutiDepartment of Emergency and Critical Care Medicine, Children's Hospital of Fudan University, Shanghai Institute of Infectious Disease and Biosecurity, and Institutes of Biomedical Sciences Fudan University, 200032, Shanghai, China.
Hetian ZhouDepartment of Emergency and Critical Care Medicine, Children's Hospital of Fudan University, Shanghai Institute of Infectious Disease and Biosecurity, and Institutes of Biomedical Sciences Fudan University, 200032, Shanghai, China.
Wenjia TongDepartment of Pediatric Critical Care Unit, Anhui Provincial Children's Hospital, Hefei, China.
Zhenhao YuDepartment of Emergency and Critical Care Medicine, Children's Hospital of Fudan University, Shanghai Institute of Infectious Disease and Biosecurity, and Institutes of Biomedical Sciences Fudan University, 200032, Shanghai, China.
Yao WangCenter for Molecular Medicine, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
Guoyun SuPediatric Intensive Care Unit, Shenzhen Children's Hospital, Shenzhen, China.
Weiguo YangPediatric Intensive Care Unit, Shenzhen Children's Hospital, Shenzhen, China.
Yufeng ZhouDepartment of Emergency and Critical Care Medicine, Children's Hospital of Fudan University, Shanghai Institute of Infectious Disease and Biosecurity, and Institutes of Biomedical Sciences Fudan University, 200032, Shanghai, China. yfzhou1@fudan.edu.cn.ORCID http://orcid.org/0000-0002-6050-4951
Guoping LuDepartment of Emergency and Critical Care Medicine, Children's Hospital of Fudan University, Shanghai Institute of Infectious Disease and Biosecurity, and Institutes of Biomedical Sciences Fudan University, 200032, Shanghai, China. lgp@fudan.edu.cn.ORCID http://orcid.org/0000-0002-5244-3781
Caiyan ZhangDepartment of Emergency and Critical Care Medicine, Children's Hospital of Fudan University, Shanghai Institute of Infectious Disease and Biosecurity, and Institutes of Biomedical Sciences Fudan University, 200032, Shanghai, China. zhangcy17@fudan.edu.cn.ORCID http://orcid.org/0000-0001-9818-1468

Funding

National Natural Science Foundation of China (National Science Foundation of China) 81974248National Natural Science Foundation of China (National Science Foundation of China) 82241038National Natural Science Foundation of China (National Science Foundation of China) 82372168
6 · The paper itself

Abstract

Acute thymic involution (ATI) is frequently observed during sepsis, however the underlying mechanisms remain poorly understood. This study demonstrates that ferroptosis plays a crucial role in sepsis-associated ATI. We found that pediatric sepsis patients showed significantly elevated kynurenine (Kyn)/tryptophan (Trp) ratios, indicating increased indoleamine 2,3-dioxygenase 1 (IDO1) activity, along with higher Kyn levels compared to controls. Moreover, Kyn levels were negatively correlated with thymus-to-thorax ratio. Further mechanistic analysis revealed that the enhanced expression of IDO1, induced by inflammatory signals, drives the accumulation of Kyn and subsequent activation of the aryl hydrocarbon receptor (AhR), triggering lipid oxidation-related gene transcription and ferroptosis in thymocytes during sepsis. Treatment with 1-methyltryptophan (IDO1 inhibitor) effectively restore thymic function and improve survival in septic mice. Our findings reveal a novel role for the IDO1/Kyn/AhR pathway in ferroptosis, suggesting that targeting this pathway may offer a promising therapeutic strategy for sepsis. Created with BioRender ( https://app.biorender.com/ ).

Indexed as

FerroptosisIndoleamine-Pyrrole 2,3,-DioxygenaseKynurenineReceptors, Aryl HydrocarbonSepsisThymus GlandAnimalsChildFemaleHumansMaleMiceMice, Inbred C57BLSignal TransductionTryptophanIDO1 protein, humanIDO1 protein, mouseIndoleamine-Pyrrole 2,3,-DioxygenaseKynurenineReceptors, Aryl HydrocarbonTryptophan

Identifiers

PMID40715082
PMCPMC12297531

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.