Evidence map›Paper›PMID 38907105›Full record

ArticleCommunications biology2024

IL-37d suppresses Rheb-mTORC1 axis independently of TCS2 to alleviate alcoholic liver disease.

Nuo Chen, Xiaoyu Wang, Yaxin Guo, Ming Zhao, Baihui Cao, Bing Zhan, Yubin Li, Tian Zhou, Faliang Zhu, Chun Guo and 4 more

Abstract read
In one paragraph

Article in Communications biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Interleukin-18 armours antitumour immune effectors.Nature reviews. Immunology · 2026
    Review
  3. Article
  4. Review
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

14 authors.

Nuo ChenDepartment of Immunology, School of Basic Medical Science, Shandong University, Jinan, China.
Xiaoyu WangDepartment of Immunology, School of Basic Medical Science, Shandong University, Jinan, China.
Yaxin GuoDepartment of Immunology, School of Basic Medical Science, Shandong University, Jinan, China.
Ming ZhaoDepartment of Immunology, School of Basic Medical Science, Shandong University, Jinan, China.
Baihui CaoDepartment of Immunology, School of Basic Medical Science, Shandong University, Jinan, China.
Bing ZhanDepartment of Immunology, School of Basic Medical Science, Shandong University, Jinan, China.
Yubin LiDepartment of Immunology, School of Basic Medical Science, Shandong University, Jinan, China.
Tian ZhouDepartment of Immunology, School of Basic Medical Science, Shandong University, Jinan, China.
Faliang ZhuDepartment of Immunology, School of Basic Medical Science, Shandong University, Jinan, China.
Chun GuoDepartment of Immunology, School of Basic Medical Science, Shandong University, Jinan, China.
Yongyu ShiDepartment of Immunology, School of Basic Medical Science, Shandong University, Jinan, China.
Qun WangDepartment of Immunology, School of Basic Medical Science, Shandong University, Jinan, China.
Lining ZhangDepartment of Immunology, School of Basic Medical Science, Shandong University, Jinan, China. zhanglining@sdu.edu.cn.ORCID 0000-0002-8977-1148
Yan LiDepartment of Pathogen Biology, School of Basic Medical Science, Shandong University, Jinan, China. liyan2015@sdu.edu.cn.ORCID 0000-0002-9521-3265

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Tuberous sclerosis complex 2 (TSC2) crucially suppresses Rheb activity to prevent mTORC1 activation. However, mutations in TSC genes lead to mTORC1 overactivation, thereby causing various developmental disorders and cancer. Therefore, the discovery of novel Rheb inhibitors is vital to prevent mTOR overactivation. Here, we reveals that the anti-inflammatory cytokine IL-37d can bind to lysosomal Rheb and suppress its activity independent of TSC2, thereby preventing mTORC1 activation. The binding of IL-37d to Rheb switch-II subregion destabilizes the Rheb-mTOR and mTOR-S6K interactions, further halting mTORC1 signaling. Unlike TSC2, IL-37d is reduced under ethanol stimulation, which results in mitigating the suppression of lysosomal Rheb-mTORC1 activity. Consequently, the recombinant human IL-37d protein (rh-IL-37d) with a TAT peptide greatly improves alcohol-induced liver disorders by hindering Rheb-mTORC1 axis overactivation in a TSC2- independent manner. Together, IL-37d emerges as a novel Rheb suppressor independent of TSC2 to terminate mTORC1 activation and improve abnormal lipid metabolism in the liver.

Indexed as

Liver Diseases, AlcoholicMechanistic Target of Rapamycin Complex 1Ras Homolog Enriched in Brain ProteinSignal TransductionTuberous Sclerosis Complex 2 ProteinAnimalsHEK293 CellsHumansInterleukin-1MaleMiceMice, Inbred C57BLInterleukin-1Mechanistic Target of Rapamycin Complex 1Ras Homolog Enriched in Brain ProteinRHEB protein, humanRheb protein, mouseTuberous Sclerosis Complex 2 Protein

Identifiers

PMID38907105
PMCPMC11192940

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.