Frequency of IRF5+ dendritic cells is associated with the TLR7-induced inflammatory cytokine response in SARS-CoV-2 infection
The SARS-CoV-2 infection leads to enhanced inflammation driven by innate immune responses. Upon TLR7 stimulation, dendritic cells (DC) mediate the production of inflammatory cytokines, and in particular of type I interferons (IFN). Especially in DCs, IRF5 is a key transcription factor that regulates...
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| Hauptverfasser: | , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
February 2023
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| In: |
Cytokine
Year: 2023, Jahrgang: 162, Pages: 1-9 |
| ISSN: | 1096-0023 |
| DOI: | 10.1016/j.cyto.2022.156109 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.cyto.2022.156109 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S1043466622003180 
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| Verfasserangaben: | Leon Cords, Robin Woost, Silke Kummer, Thomas T. Brehm, Stefan Kluge, Stefan Schmiedel, Sabine Jordan, Ansgar W. Lohse, Marcus Altfeld, Marylyn M. Addo, Julian Schulze zur Wiesch, Claudia Beisel |
MARC
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| 245 | 1 | 0 | |a Frequency of IRF5+ dendritic cells is associated with the TLR7-induced inflammatory cytokine response in SARS-CoV-2 infection |c Leon Cords, Robin Woost, Silke Kummer, Thomas T. Brehm, Stefan Kluge, Stefan Schmiedel, Sabine Jordan, Ansgar W. Lohse, Marcus Altfeld, Marylyn M. Addo, Julian Schulze zur Wiesch, Claudia Beisel |
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| 500 | |a Published: 13 December 2022 | ||
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| 520 | |a The SARS-CoV-2 infection leads to enhanced inflammation driven by innate immune responses. Upon TLR7 stimulation, dendritic cells (DC) mediate the production of inflammatory cytokines, and in particular of type I interferons (IFN). Especially in DCs, IRF5 is a key transcription factor that regulates pathogen-induced immune responses via activation of the MyD88-dependent TLR signaling pathway. In the current study, the frequencies of IRF5+ DCs and the association with innate cytokine responses in SARS-CoV-2 infected individuals with different disease courses were investigated. In addition to a decreased number of mDC and pDC subsets, we could show reduced relative IRF5+ frequencies in mDCs of SARS-CoV-2 infected individuals compared with healthy donors. Functionally, mDCs of COVID-19 patients produced lower levels of IL-6 in response to in vitro TLR7 stimulation. IRF5+ mDCs more frequently produced IL-6 and TNF-α compared to their IRF5− counterparts upon TLR7 ligation. The correlation of IRF5+ mDCs with the frequencies of IL-6 and TNF-α producing mDCs were indicators for a role of IRF5 in the regulation of cytokine responses in mDCs. In conclusion, our data provide further insights into the underlying mechanisms of TLR7-dependent immune dysfunction and identify IRF5 as a potential immunomodulatory target in SARS-CoV-2 infection. | ||
| 650 | 4 | |a Dendritic cells | |
| 650 | 4 | |a Interferon regulatory factor 5 | |
| 650 | 4 | |a Interferon-α | |
| 650 | 4 | |a Interleukin-6 | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a Toll-like receptor 7 | |
| 650 | 4 | |a Tumor necrosis factor-α | |
| 700 | 1 | |a Woost, Robin |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kummer, Silke |e VerfasserIn |4 aut | |
| 700 | 1 | |a Brehm, Thomas T. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kluge, Stefan |e VerfasserIn |4 aut | |
| 700 | 1 | |a Schmiedel, Stefan |e VerfasserIn |4 aut | |
| 700 | 1 | |a Jordan, Sabine |e VerfasserIn |4 aut | |
| 700 | 1 | |a Lohse, Ansgar W. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Altfeld, Marcus |e VerfasserIn |4 aut | |
| 700 | 1 | |a Addo, Marylyn M. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Schulze zur Wiesch, Julian |e VerfasserIn |4 aut | |
| 700 | 1 | |a Beisel, Claudia |d 1982- |e VerfasserIn |0 (DE-588)1015931286 |0 (DE-627)66990709X |0 (DE-576)351301968 |4 aut | |
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