VEGF-A enhances the cytotoxic function of CD4+ cytotoxic T cells via the VEGF-receptor 1/VEGF-receptor 2/AKT/mTOR pathway
© 2023. The Author(s)..
BACKGROUND: CD4+ cytotoxic T cells (CD4 CTLs) are CD4+ T cells with major histocompatibility complex-II-restricted cytotoxic function. Under pathologic conditions, CD4 CTLs hasten the development of autoimmune disease or viral infection by enhancing cytotoxicity. However, the regulators of the cytotoxicity of CD4 CTLs are not fully understood.
METHODS: To explore the potential regulators of the cytotoxicity of CD4 CTLs, bulk RNA and single-cell RNA sequencing (scRNA-seq), enzyme-linked immunosorbent assay, flow cytometry, quantitative PCR, and in-vitro stimulation and inhibition assays were performed.
RESULTS: In this study, we found that VEGF-A promoted the cytotoxicity of CD4 CTLs through scRNA-seq and flow cytometry. Regarding the specific VEGF receptor (R) involved, VEGF-R1/R2 signaling was activated in CD4 CTLs with increased cytotoxicity, and the VEGF-A effects were inhibited when anti-VEGF-R1/R2 neutralizing antibodies were applied. Mechanistically, VEGF-A treatment activated the AKT/mTOR pathway in CD4 CTLs, and the increases of cytotoxic molecules induced by VEGF-A were significantly reduced when the AKT/mTOR pathway was inhibited.
CONCLUSION: In conclusion, VEGF-A enhances the cytotoxicity of CD4 CTLs through the VEGF-R1/VEGF-R2/AKT/mTOR pathway, providing insights for the development of novel treatments for disorders associated with CD4 CTLs.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:21 |
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| Enthalten in: |
Journal of translational medicine - 21(2023), 1 vom: 03. Feb., Seite 74 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chen, Ziyi [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 09.02.2023 Date Revised 15.02.2023 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1186/s12967-023-03926-w |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM352478403 |
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| 100 | 1 | |a Chen, Ziyi |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a VEGF-A enhances the cytotoxic function of CD4+ cytotoxic T cells via the VEGF-receptor 1/VEGF-receptor 2/AKT/mTOR pathway |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Completed 09.02.2023 | ||
| 500 | |a Date Revised 15.02.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023. The Author(s). | ||
| 520 | |a BACKGROUND: CD4+ cytotoxic T cells (CD4 CTLs) are CD4+ T cells with major histocompatibility complex-II-restricted cytotoxic function. Under pathologic conditions, CD4 CTLs hasten the development of autoimmune disease or viral infection by enhancing cytotoxicity. However, the regulators of the cytotoxicity of CD4 CTLs are not fully understood | ||
| 520 | |a METHODS: To explore the potential regulators of the cytotoxicity of CD4 CTLs, bulk RNA and single-cell RNA sequencing (scRNA-seq), enzyme-linked immunosorbent assay, flow cytometry, quantitative PCR, and in-vitro stimulation and inhibition assays were performed | ||
| 520 | |a RESULTS: In this study, we found that VEGF-A promoted the cytotoxicity of CD4 CTLs through scRNA-seq and flow cytometry. Regarding the specific VEGF receptor (R) involved, VEGF-R1/R2 signaling was activated in CD4 CTLs with increased cytotoxicity, and the VEGF-A effects were inhibited when anti-VEGF-R1/R2 neutralizing antibodies were applied. Mechanistically, VEGF-A treatment activated the AKT/mTOR pathway in CD4 CTLs, and the increases of cytotoxic molecules induced by VEGF-A were significantly reduced when the AKT/mTOR pathway was inhibited | ||
| 520 | |a CONCLUSION: In conclusion, VEGF-A enhances the cytotoxicity of CD4 CTLs through the VEGF-R1/VEGF-R2/AKT/mTOR pathway, providing insights for the development of novel treatments for disorders associated with CD4 CTLs | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a CD4 CTLs | |
| 650 | 4 | |a CD4+ cytotoxic T cells | |
| 650 | 4 | |a Graves orbitopathy | |
| 650 | 4 | |a VEGF-A | |
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| 700 | 1 | |a Zhang, Meng |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yufeng |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Zhe |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Ling |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Wenjuan |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jincheng |e verfasserin |4 aut | |
| 700 | 1 | |a He, Mingqian |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Bingyin |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yue |e verfasserin |4 aut | |
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