Evidence mapPaperPMID 41933939Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

Legumain Restrains Granuloma Formation by Inhibiting mTORC1/STAT1-Mediated M1 Macrophage Polarization in Sarcoidosis.

Mengyuan Liu, Yueyin Han, Bingbing Xie, Lili Zhu, Wenxiu Xu, Yinzhen Han, Yue Liao, Shuwei Gao, Dingyuan Jiang, Jing Geng and 3 more

Abstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. 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.

Mengyuan LiuChina-Japan Friendship Hospital (Institute of Clinical Medical Sciences), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.ORCID https://orcid.org/0009-0008-9833-7547
Yueyin HanChina-Japan Friendship Hospital (Institute of Clinical Medical Sciences), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Bingbing XieNational Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China.
Lili ZhuNational Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China.
Wenxiu XuNational Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China.
Yinzhen HanChina-Japan Friendship Hospital (Institute of Clinical Medical Sciences), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Yue LiaoChina-Japan Friendship Hospital (Institute of Clinical Medical Sciences), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Shuwei GaoNational Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China.
Dingyuan JiangNational Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China.
Jing GengNational Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China.
Zhen LiDepartment of Pulmonary and Critical Care Medicine, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Science, Beijing, China.
Yinan HuNational Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China.
Huaping DaiChina-Japan Friendship Hospital (Institute of Clinical Medical Sciences), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.ORCID https://orcid.org/0000-0003-1124-1582

Funding

Beijing Nova Program 20230484281Capital's Funds for Health Improvement and Research 2024-1-4062National High Level Hospital Clinical Research Funding BJ-2024-251National Natural Science Foundation of China 82170080National Natural Science Foundation of China 82370072National Natural Science Foundation of China 82500089State Key Laboratory Special Fund 2060204
6 · The paper itself

Abstract

Sarcoidosis is a systemic granulomatous disease that has limited treatment options. Emerging evidence suggests that macrophages are essential for sarcoid granuloma initiation. Legumain (LGMN), a cysteine protease, regulates macrophage polarization in various cancers. However, its involvement in sarcoid granuloma formation remains elusive. Herein, LGMN is upregulated in macrophages within sarcoid-like granulomas. Genetic deletion of Lgmn exacerbates granulomatous inflammation in a Propionibacterium acnes (P. acnes)-induced mouse model, accompanied by increased M1 macrophage polarization. Mechanistically, LGMN binds to integrin αvβ3 on the macrophage surface and restrains M1 polarization by inhibiting the mechanistic target of rapamycin complex 1 (mTORC1)/signal transducer and activator of transcription 1 (STAT1) pathway. Furthermore, intratracheal administration of lipid nanoparticles carrying Lgmn plasmid DNA effectively alleviates granuloma formation induced by P. acnes or trehalose 6,6'-dimycolate, concomitant with decreased mTORC1/STAT1 activation and M1 polarization. These findings reveal the pivotal role of LGMN in restraining sarcoid granulomatous inflammation through suppression of mTORC1/STAT1-driven M1 macrophage polarization. Therefore, LGMN supplementation may be a promising therapeutic strategy for sarcoidosis.

Indexed as

Cysteine EndopeptidasesGranulomaMacrophagesMechanistic Target of Rapamycin Complex 1SarcoidosisSTAT1 Transcription FactorAnimalsAsparaginyl EndopeptidaseDisease Models, AnimalHumansMiceSignal TransductionAsparaginyl EndopeptidaseCysteine EndopeptidasesMechanistic Target of Rapamycin Complex 1Stat1 protein, mouseSTAT1 Transcription Factorgranulomaslegumainlipid nanoparticlesmacrophagessarcoidosis

Identifiers

PMID41933939
PMCPMC13271614

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.