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Cited by 24Viral Infections and Immunology ResearchNeutrophil, Myeloperoxidase and Oxidative MechanismsVasculitis and related conditions

Inhibition of NETosis via PAD4 alleviated inflammation in giant cell myocarditis

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Hu, Zhan, Hua, Xiumeng, Mo, Xiuxue, Chang, Yuan, Chen, Xiao, Xu, Zhenyu, Tao, Mengtao, Hu, Gang +1 more·2023·iScience
DOI 10.1016/j.isci.2023.107162PMC PMC10391931
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Abstract

Giant cell myocarditis (GCM) is a rare, usually rapidly progressive, and potentially fatal disease. Detailed inflammatory responses remain unknown, in particular the formation of multinucleate giant cells. We performed single-cell RNA sequencing analysis on 15,714 Cd45 + cells extracted from the hearts of GCM rats and normal rats. NETosis has been found to contribute to the GCM process. An inhibitor of NETosis, GSK484, alleviated GCM inflammation in vivo . MPO (a marker of neutrophils) and H3cit (a marker of NETosis) were expressed at higher levels in patients with GCM than in patients with DCM and healthy controls. Imaging mass cytometry analysis revealed that immune cell types within multinucleate giant cells included CD4 + T cells, CD8 + T cells, neutrophils, and macrophages but not B cells. We elucidated the role of NETosis in GCM pathogenesis, which may serve as a potential therapeutic target in the clinic.

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  • Multinucleated giant cells might originate from a particular macrophage subset expressing transmembrane GPNMB.

    “multinucleated giant cells might originate from a particular macrophage subset expressing transmembrane GPNMB (glycoprotein NMB).”

    From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [193]

    In Results, “Two specific macrophage clusters involved in GCM have roles in phagocytosis” (page unavailable), Gpnmb is listed as a marker of monocyte-derived macrophages. The IMC Results section (page unavailable) reports that one pattern of multinucleated giant cells was primarily composed of macrophages. The paper does not establish that the giant cells originate specifically from the Gpnmb-expressing subset. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • In the cardiac myosin-immunized rat model, a majority of cardiac infiltrating T cells are CD4+ T cells expressing Il17a and Il22.

    “a single-cell analysis approach revealed that a majority of cardiac infiltrating T cells are CD4 + T cells expressing Il17a and Il22 in this model.”

    From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [193]

  • Macrophages with heterogeneous origins constitute the largest immune cell population in giant cell myocarditis.

    “macrophages, with heterogeneous origins, constituted the largest immune cell population in giant cell myocarditis”

    From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [193]

  • Neutrophils may play a pathogenic role through the formation of neutrophil extracellular traps in giant cell myocarditis.

    “there is evidence suggesting a pathogenic role of neutrophils through the formation of neutrophil extracellular traps in giant cell myocarditis”

    From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [193]

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Authors
Hu, Z., Hua, X., Mo, X., Chang, Y., Chen, X., Xu, Z., Tao, M., Hu, G., & Song, J.
Affiliations
  • Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
  • Nankai University (CN)
Corresponding author
  • Hu, Gang
  • Song, Jiangping
ORCID
Venue
iScience
Publisher
Elsevier BV
Published
2023-07
Volume
26
Issue
7
Pages
107162
ISSN
2589-0042 (ISSN-L)
DOI
10.1016/j.isci.2023.107162
PMC
PMC10391931
OpenAlex
W4380991051
Cited by
24
References
74
Citations by year
2026: 10 · 2025: 7 · 2024: 7
FWCI
4.72
Type
journal article
Language
en
Open access
Licence
Locations
  • iScience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Beijing Nova Program (Z20110006820003)
  • China National Funds for Distinguished Young Scientists (82125004)
  • Chinese Academy of Medical Sciences & Peking Union Medical College Fuwai Hospital
  • Fundamental Research Funds for the Central Universities
  • Beijing Municipal Commission of Education (KJZD20191002301)
  • National Natural Science Foundation of China (81900335)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Viral Infections and Immunology Research
  • Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Vasculitis and related conditions
Keywords
giant cell myocarditis, NETosis, PAD4, GSK484, neutrophil extracellular traps, myocarditis, multinucleated giant cells, neutrophils, CD4+ T cells, CD8+ T cells, macrophages, histone H3 citrullination, therapeutic target

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