Anti‐CTLA‐4 m2a Antibody Exacerbates Cardiac Injury in Experimental Autoimmune Myocarditis Mice By Promoting Ccl5‐Neutrophil Infiltration Article Swipe
Ming‐Ming Wu
,
Yan‐Chao Yang
,
Yong‐Xu Cai
,
Shuai Jiang
,
Han Xiao
,
Miao Chang
,
Xi‐Yun Jin
,
Yu Sun
,
Xin Bi
,
Zi Hong
,
Di Zhu
,
Miao Yu
,
Jian‐Jun Mao
,
Changjiang Yu
,
Liang Chen
,
Liang‐Liang Tang
,
Qiushi Wang
,
Qun Shao
,
Qing‐Hua Jiang
,
Zhenwei Pan
,
Zhi‐Ren Zhang
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1002/advs.202400486
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1002/advs.202400486
The risk for suffering immune checkpoint inhibitors (ICIs)‐associated myocarditis increases in patients with pre‐existing conditions and the mechanisms remain to be clarified. Spatial transcriptomics, single‐cell RNA sequencing, and flow cytometry are used to decipher how anti‐cytotoxic T lymphocyte antigen‐4 m2a antibody (anti‐CTLA‐4 m2a antibody) aggravated cardiac injury in experimental autoimmune myocarditis (EAM) mice. It is found that anti‐CTLA‐4 m2a antibody increases cardiac fibroblast‐derived C‐X‐C motif chemokine ligand 1 (Cxcl1), which promots neutrophil infiltration to the myocarditic zones (MZs) of EAM mice via enhanced Cxcl1‐Cxcr2 chemotaxis. It is identified that the C–C motif chemokine ligand 5 (Ccl5)‐neutrophil subpopulation is responsible for high activity of cytokine production, adaptive immune response, NF‐κB signaling, and cellular response to interferon‐gamma and that the Ccl5‐neutrophil subpopulation and its‐associated proinflammatory cytokines/chemokines promoted macrophage (Mφ) polarization to M1 Mφ. These altered infiltrating landscape and phenotypic switch of immune cells, and proinflammatory factors synergistically aggravated anti‐CTLA‐4 m2a antibody‐induced cardiac injury in EAM mice. Neutralizing neutrophils, Cxcl1, and applying Cxcr2 antagonist dramatically alleviates anti‐CTLA‐4 m2a antibody‐induced leukocyte infiltration, cardiac fibrosis, and dysfunction. It is suggested that Ccl5‐neutrophil subpopulation plays a critical role in aggravating anti‐CTLA‐4 m2a antibody‐induced cardiac injury in EAM mice. This data may provide a strategic rational for preventing/curing ICIs‐associated myocarditis.
Related Topics
Concepts
Chemokine
Proinflammatory cytokine
Immunology
CCL5
Immune system
CXCL1
Antibody
T cell
Inflammation
Chemistry
Medicine
IL-2 receptor
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1002/advs.202400486
- OA Status
- gold
- Cited By
- 11
- References
- 39
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4400473283
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4400473283Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1002/advs.202400486Digital Object Identifier
- Title
-
Anti‐CTLA‐4 m2a Antibody Exacerbates Cardiac Injury in Experimental Autoimmune Myocarditis Mice By Promoting Ccl5‐Neutrophil InfiltrationWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-07-08Full publication date if available
- Authors
-
Ming‐Ming Wu, Yan‐Chao Yang, Yong‐Xu Cai, Shuai Jiang, Han Xiao, Miao Chang, Xi‐Yun Jin, Yu Sun, Xin Bi, Zi Hong, Di Zhu, Miao Yu, Jian‐Jun Mao, Changjiang Yu, Liang Chen, Liang‐Liang Tang, Qiushi Wang, Qun Shao, Qing‐Hua Jiang, Zhenwei Pan, Zhi‐Ren ZhangList of authors in order
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https://doi.org/10.1002/advs.202400486Publisher landing page
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YesWhether a free full text is available
- OA status
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goldOpen access status per OpenAlex
- OA URL
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https://doi.org/10.1002/advs.202400486Direct OA link when available
- Concepts
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Chemokine, Proinflammatory cytokine, Immunology, CCL5, Immune system, CXCL1, Antibody, T cell, Inflammation, Chemistry, Medicine, IL-2 receptorTop concepts (fields/topics) attached by OpenAlex
- Cited by
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11Total citation count in OpenAlex
- Citations by year (recent)
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2025: 8, 2024: 3Per-year citation counts (last 5 years)
- References (count)
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39Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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