Evidence map›Paper›PMID 41474968›Full record

ArticleThe Journal of experimental medicine2026

Tet2 deficiency-induced expansion of monocyte-derived macrophages promotes liver fibrosis.

Jiuxing Feng, Baitong Wu, Yu Li, Pengli Sun, Qian Liu, Qianxue Xiao, Jia-Bin Cai, Yimin Zheng, Haonan Chen, Yichi Xu and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of experimental medicine, 2026. 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. Article
  2. Review
  3. Review
  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.

Jiuxing Feng *The Shanghai Key Laboratory of Medical Epigenetics, Liver Cancer Institute, Institutes of Biomedical Sciences and Zhongshan Hospital, Fudan University , Shanghai, P.R. China.ORCID 0009-0008-3003-4099
Baitong Wu *East Hospital, Stem Cell Research Center, School of Medicine, Tongji University , Shanghai, P.R. China.ORCID 0000-0001-7911-7145
Yu LiThe Shanghai Key Laboratory of Medical Epigenetics, Liver Cancer Institute, Institutes of Biomedical Sciences and Zhongshan Hospital, Fudan University , Shanghai, P.R. China.ORCID 0000-0001-8016-2242
Pengli SunThe Shanghai Key Laboratory of Medical Epigenetics, Liver Cancer Institute, Institutes of Biomedical Sciences and Zhongshan Hospital, Fudan University , Shanghai, P.R. China.ORCID 0009-0004-5171-1299
Qian LiuThe Shanghai Key Laboratory of Medical Epigenetics, Liver Cancer Institute, Institutes of Biomedical Sciences and Zhongshan Hospital, Fudan University , Shanghai, P.R. China.ORCID 0009-0006-8485-5648
Qianxue XiaoThe Shanghai Key Laboratory of Medical Epigenetics, Liver Cancer Institute, Institutes of Biomedical Sciences and Zhongshan Hospital, Fudan University , Shanghai, P.R. China.ORCID 0009-0005-4851-4240
Jia-Bin CaiThe Shanghai Key Laboratory of Medical Epigenetics, Liver Cancer Institute, Institutes of Biomedical Sciences and Zhongshan Hospital, Fudan University , Shanghai, P.R. China.ORCID 0000-0002-2930-5532
Yimin ZhengThe Shanghai Key Laboratory of Medical Epigenetics, Liver Cancer Institute, Institutes of Biomedical Sciences and Zhongshan Hospital, Fudan University , Shanghai, P.R. China.ORCID 0000-0002-4701-945X
Haonan ChenThe Shanghai Key Laboratory of Medical Epigenetics, Liver Cancer Institute, Institutes of Biomedical Sciences and Zhongshan Hospital, Fudan University , Shanghai, P.R. China.ORCID 0000-0002-4147-5040
Yichi XuDepartment of Biomedical Engineering, Cornell University, Ithaca, NY, USA.ORCID 0009-0003-6808-6832
Yixin LiuThe Shanghai Key Laboratory of Medical Epigenetics, Liver Cancer Institute, Institutes of Biomedical Sciences and Zhongshan Hospital, Fudan University , Shanghai, P.R. China.ORCID 0009-0005-6474-9787
Guo-Ming ShiThe Shanghai Key Laboratory of Medical Epigenetics, Liver Cancer Institute, Institutes of Biomedical Sciences and Zhongshan Hospital, Fudan University , Shanghai, P.R. China.ORCID 0000-0003-3817-9117
Li TanThe Shanghai Key Laboratory of Medical Epigenetics, Liver Cancer Institute, Institutes of Biomedical Sciences and Zhongshan Hospital, Fudan University , Shanghai, P.R. China.ORCID 0000-0001-5961-0450
Yujiang Geno ShiThe Shanghai Key Laboratory of Medical Epigenetics, Liver Cancer Institute, Institutes of Biomedical Sciences and Zhongshan Hospital, Fudan University , Shanghai, P.R. China.ORCID 0009-0004-5552-4976

Funding

China Postdoctoral Science Foundation GZC20231944China Postdoctoral Science Foundation KLF1340024Fudan University JIH1340084YFudan University JIH1340107YNational Natural Science Foundation of China 82073113
6 · The paper itself

Abstract

Clonal hematopoiesis driven by Tet2 deficiency in myeloid cells (TetΔMye) is prevalent in elderly individuals; however, the role of Tet2ΔMye in liver fibrosis pathogenesis remains elusive. In this study, we demonstrated that Tet2-deficient monocyte-derived macrophages (MDMs) promoted cellular expansion and elevated C-C motif chemokine ligand 2/8 (Ccl2/8) secretion by stabilizing their mRNAs through 5hmC-mediated alterations in RNA-protein interactions. These chemokines engaged with the upregulated C-C motif chemokine receptor (Ccr2/3) on Tet2-/- monocytes, forming a positive feedback loop that amplified pro-inflammatory MDMs (pMDMs) accumulation in liver. Tet2-/- pMDMs activated hepatic stellate cells through IL-6, driving extracellular matrix deposition and fibrotic progression. Pharmacological inhibition of Ccl2/Ccl8 with Bindarit attenuated MDMs accumulation and liver fibrosis, whereas combined therapy with Bindarit and IL-6 neutralization synergistically suppressed liver fibrosis in Tet2ΔMye mice and aged chimeric models recapitulating Tet2ΔMye-related myeloid hematopoiesis. These findings present the mechanism that Tet2ΔMye aggravates liver fibrosis and highlight MDMs depletion plus IL-6 neutralization as a promising therapy for liver fibrosis in patients with Tet2ΔMye-related myeloid hematopoiesis.

Indexed as

DNA-Binding ProteinsLiver CirrhosisMacrophagesMonocytesProto-Oncogene ProteinsAnimalsCell ProliferationDioxygenasesHepatic Stellate CellsHumansInterleukin-6LiverMaleMiceMice, Inbred C57BLMice, KnockoutDioxygenasesDNA-Binding ProteinsInterleukin-6Proto-Oncogene ProteinsReceptors, CCR2Tet2 protein, mouse

Identifiers

PMID41474968
PMCPMC12755866

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.