Evidence map›Paper›PMID 41136987›Full record

ArticleCell communication and signaling : CCS2025

Epigenetic reprogramming of dendritic cells by DNMT1 inhibition attenuates Th2 skewing in allergic airway inflammation.

Jinmei Xue, Yisha Wu, Zhizhen Liu, Siyu Duan, Yongjin Ji, Rui Dong, Lei Lu, Fangling Guan, Zhigang Geng, Yun Li and 3 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Cell communication and signaling : CCS, 2025. 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

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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

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3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

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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.

Jinmei XueDepartment of Otolaryngology, Head and Neck Surgery, Second Hospital, Shanxi Medical University, Taiyuan, 030001, China.
Yisha WuDepartment of Otolaryngology, Head and Neck Surgery, Second Hospital, Shanxi Medical University, Taiyuan, 030001, China.
Zhizhen LiuDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention, Shanxi Medical University, Taiyuan, China.
Siyu DuanDepartment of Otolaryngology, Head and Neck Surgery, Second Hospital, Shanxi Medical University, Taiyuan, 030001, China.
Yongjin JiDepartment of Otolaryngology, Head and Neck Surgery, Second Hospital, Shanxi Medical University, Taiyuan, 030001, China.
Rui DongDepartment of Otolaryngology, Head and Neck Surgery, Second Hospital, Shanxi Medical University, Taiyuan, 030001, China.
Lei LuDepartment of Otolaryngology, Head and Neck Surgery, Second Hospital, Shanxi Medical University, Taiyuan, 030001, China.
Fangling GuanDepartment of Otolaryngology, Head and Neck Surgery, Second Hospital, Shanxi Medical University, Taiyuan, 030001, China.
Zhigang GengDepartment of Otolaryngology, Head and Neck Surgery, Second Hospital, Shanxi Medical University, Taiyuan, 030001, China.
Yun LiDepartment of Otolaryngology, Head and Neck Surgery, Second Hospital, Shanxi Medical University, Taiyuan, 030001, China.
Jiaqi DuanState Key Laboratory of Respiratory Diseases Allergy Division, Institute of Allergy & Immunology, Shenzhen Key Laboratory of Allergy & Immunology, Shenzhen University, Shenzhen University School of Medicine, Room A7-509 at Lihu Campus of Shenzhen University, 1066 Xueyuan Blvd, Shenzhen, 518055, China.
Jun XieDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention, Shanxi Medical University, Taiyuan, China. junxie@sxmu.edu.cn.
Pingchang YangState Key Laboratory of Respiratory Diseases Allergy Division, Institute of Allergy & Immunology, Shenzhen Key Laboratory of Allergy & Immunology, Shenzhen University, Shenzhen University School of Medicine, Room A7-509 at Lihu Campus of Shenzhen University, 1066 Xueyuan Blvd, Shenzhen, 518055, China. pcy2356@163.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAllergic asthma is driven by Th2-polarized immune responses, yet the epigenetic mechanisms underlying dendritic cell (DC)-mediated Th2 skewing remain unclear.

methodsUsing a house dust mite (DME)-induced murine asthma model, we combined pharmacological DNMT1 inhibition (5-Aza-2′-deoxycytidine, 5-azadC), DC-specific Dnmt1 ablation (Dnmt1fl/fl Itgax-Cre mice), chromatin immunoprecipitation (ChIP), RT-qPCR, and ubiquitination assays to dissect methylation-dependent regulation of IL-12b and TIM4 in DCs.

resultsSensitization increased DNMT1 occupancy at the Il12b promoter, inducing hypermethylation (2.5-fold vs. naïve, p < 0.001) and suppressing IL-12b expression (60% reduction, p < 0.001). DNMT1 inhibition with 5-azadC or genetic Dnmt1 ablation restored IL-12b levels (p < 0.01), reduced BALF Th2 cytokines (40–60%), eosinophils (62%), and mast cell mediators (p < 0.01), and attenuated airway inflammation. IL-12b promoted TIM4 degradation via Trim28-mediated K48-linked ubiquitination (p < 0.01), while Il12b deficiency sustained TIM4 expression and Th2 polarization. DNMT1 enrichment at the Il12b promoter correlated with TIM4 upregulation (r = 0.87, p < 0.01), forming a self-reinforcing loop disrupted by Timd4 knockdown.

conclusionDNMT1 in DCs orchestrates Th2 polarization via Il12b silencing and TIM4 stabilization, positioning DNMT1 inhibitors and TIM4-targeted therapies as novel strategies to rebalance Th1/Th2 responses in asthma.

Indexed as

AsthmaDendritic CellsDNA (Cytosine-5-)-Methyltransferase 1Epigenesis, GeneticInflammationTh2 CellsAnimalsDNA MethylationMiceMice, Inbred C57BLPromoter Regions, GeneticDNA (Cytosine-5-)-Methyltransferase 1Dnmt1 protein, mouseAllergic asthmaDendritic cellsDNA methylationDNMT1IL-12bTh2 polarizationTIM4

Identifiers

PMID41136987
PMCPMC12551259

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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.