Evidence map›Paper›PMID 39350473›Full record

ArticleClinical and translational medicine2024

Trem2 acts as a non-classical receptor of interleukin-4 to promote diabetic wound healing.

Xinlin Zhu, Chao Zhang, Weiwei Jiang, Zhaoxiang Zeng, Keming Zhang, Mingwei Du, Juan Chen, Qian Wu, Wanqing Liao, Youming Chen and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical and translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 citing papers in PubMed.

  1. Review
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  6. Article
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  10. Roles of TREM2 in Alzheimer's disease.Translational neurodegeneration · 2025
    Review
  11. Article
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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

12 authors.

Xinlin ZhuDepartment of Dermatology, Shanghai Key Laboratory of Medical Mycology; The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), Shanghai Changzheng Hospital, Naval Medical University, Shanghai, China.
Chao ZhangDepartment of Dermatology, Shanghai Key Laboratory of Medical Mycology; The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), Shanghai Changzheng Hospital, Naval Medical University, Shanghai, China.
Weiwei JiangDepartment of Dermatology, Shanghai Key Laboratory of Medical Mycology; The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), Shanghai Changzheng Hospital, Naval Medical University, Shanghai, China.
Zhaoxiang ZengDepartment of Vascular Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
Keming ZhangDepartment of Dermatology, Shanghai Key Laboratory of Medical Mycology; The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), Shanghai Changzheng Hospital, Naval Medical University, Shanghai, China.
Mingwei DuDepartment of Dermatology, Shanghai Key Laboratory of Medical Mycology; The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), Shanghai Changzheng Hospital, Naval Medical University, Shanghai, China.
Juan ChenDepartment of Dermatology, Shanghai Key Laboratory of Medical Mycology; The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), Shanghai Changzheng Hospital, Naval Medical University, Shanghai, China.
Qian WuDepartment of Laboratory Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.ORCID 0000-0002-8912-0118
Wanqing LiaoDepartment of Dermatology, Shanghai Key Laboratory of Medical Mycology; The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), Shanghai Changzheng Hospital, Naval Medical University, Shanghai, China.
Youming ChenDepartment of Infectious Diseases and Immunology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Wenjie FangDepartment of Dermatology, Shanghai Key Laboratory of Medical Mycology; The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), Shanghai Changzheng Hospital, Naval Medical University, Shanghai, China.
Weihua PanDepartment of Dermatology, Shanghai Key Laboratory of Medical Mycology; The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), Shanghai Changzheng Hospital, Naval Medical University, Shanghai, China.ORCID 0000-0001-7381-5188

Funding

National Natural Science Foundation of China 82002124National Natural Science Foundation of China 82202543National Natural Science Foundation of China 82272355Project of the Ministry of Science and Technology 2022YFC2504803Shanghai Science and Technology Committee 20DZ2272000Shanghai Science and Technology Committee 21410750500
6 · The paper itself

Abstract

backgroundThe immunoglobulin superfamily protein Trem2 (triggering receptor expressed on myeloid cells 2) is primarily expressed on myeloid cells where it functions to regulate macrophage-related immune response induction. While macrophages are essential mediators of diabetic wound healing, the specific regulatory role that Trem2 plays in this setting remains to be established.

objectiveThis study was developed to explore the potential importance of Trem2 signalling in diabetic wound healing and to clarify the underlying mechanisms through which it functions. METHODS AND

resultsFollowing wound induction, diabetic model mice exhibited pronounced upregulation of Trem2 expression, which was primarily evident in macrophages. No cutaneous defects were evident in mice bearing a macrophage-specific knockout of Trem2 (T2-cKO), but they induced more pronounced inflammatory responses and failed to effectively repair cutaneous wounds, with lower levels of neovascularization, slower rates of wound closure, decreased collagen deposition following wounding. Mechanistically, we showed that interleukin (IL)-4 binds directly to Trem2, inactivating MAPK/AP-1 signalling to suppress the expression of inflammatory and chemoattractant factors. Co-culture of fibroblasts and macrophages showed that macrophages from T2-cKO mice suppressed the in vitro activation and proliferation of dermal fibroblasts through upregulation of leukaemia inhibitory factor (Lif). Injecting soluble Trem2 in vivo was also sufficient to significantly curtail inflammatory responses and to promote diabetic wound healing.

conclusionsThese analyses offer novel insight into the role of IL-4/Trem2 signalling as a mediator of myeloid cell-fibroblast crosstalk that may represent a viable therapeutic target for efforts to enhance diabetic wound healing.

Indexed as

Interleukin-4Membrane GlycoproteinsReceptors, ImmunologicWound HealingAnimalsDiabetes Mellitus, ExperimentalDisease Models, AnimalMacrophagesMaleMiceMice, Inbred C57BLMice, KnockoutIl4 protein, mouseInterleukin-4Membrane GlycoproteinsReceptors, ImmunologicTrem2 protein, mousediabetic wound healingIL‐4macrophageMAPKTrem2

Identifiers

PMID39350473
PMCPMC11442487

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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.