Profound Treg perturbations correlate with COVID-19 severity
The hallmark of severe COVID-19 disease has been an uncontrolled inflammatory response, resulting from poorly understood immunological dysfunction. We explored the hypothesis that perturbations in FoxP3+ T regulatory cells (Treg), key enforcers of immune homeostasis, contribute to COVID-19 pathology. Cytometric and transcriptomic profiling revealed a distinct Treg phenotype in severe COVID-19 patients, with an increase in both Treg proportions and intracellular levels of the lineage-defining transcription factor FoxP3, which correlated with poor outcomes. Accordingly, these Tregs over-expressed a range of suppressive effectors, but also pro-inflammatory molecules like IL32. Most strikingly, they acquired similarity to tumor-infiltrating Tregs, known to suppress local anti-tumor responses. These traits were most marked in acute patients with severe disease, but persisted somewhat in convalescent patients. These results suggest that Tregs may play nefarious roles in COVID-19, via suppressing anti-viral T cell responses during the severe phase of the disease, and/or via a direct pro-inflammatory role.
| Errataetall: |
UpdateIn: Proc Natl Acad Sci U S A. 2021 Sep 14;118(37):. - PMID 34433692 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2020 |
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| Enthalten in: |
bioRxiv : the preprint server for biology - (2020) vom: 15. Dez. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Galvan-Pena, Silvia [VerfasserIn] |
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Date Revised 14.01.2022 published: Electronic UpdateIn: Proc Natl Acad Sci U S A. 2021 Sep 14;118(37):. - PMID 34433692 Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1101/2020.12.11.416180 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM318959232 |
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| 500 | |a UpdateIn: Proc Natl Acad Sci U S A. 2021 Sep 14;118(37):. - PMID 34433692 | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a The hallmark of severe COVID-19 disease has been an uncontrolled inflammatory response, resulting from poorly understood immunological dysfunction. We explored the hypothesis that perturbations in FoxP3+ T regulatory cells (Treg), key enforcers of immune homeostasis, contribute to COVID-19 pathology. Cytometric and transcriptomic profiling revealed a distinct Treg phenotype in severe COVID-19 patients, with an increase in both Treg proportions and intracellular levels of the lineage-defining transcription factor FoxP3, which correlated with poor outcomes. Accordingly, these Tregs over-expressed a range of suppressive effectors, but also pro-inflammatory molecules like IL32. Most strikingly, they acquired similarity to tumor-infiltrating Tregs, known to suppress local anti-tumor responses. These traits were most marked in acute patients with severe disease, but persisted somewhat in convalescent patients. These results suggest that Tregs may play nefarious roles in COVID-19, via suppressing anti-viral T cell responses during the severe phase of the disease, and/or via a direct pro-inflammatory role | ||
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| 700 | 1 | |a Leon, Juliette |e verfasserin |4 aut | |
| 700 | 1 | |a Chowdhary, Kaitavjeet |e verfasserin |4 aut | |
| 700 | 1 | |a Michelson, Daniel A |e verfasserin |4 aut | |
| 700 | 1 | |a Vijaykumar, Brinda |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Liang |e verfasserin |4 aut | |
| 700 | 1 | |a Magnuson, Angela |e verfasserin |4 aut | |
| 700 | 1 | |a Manickas-Hill, Zachary |e verfasserin |4 aut | |
| 700 | 1 | |a Piechocka-Trocha, Alicja |e verfasserin |4 aut | |
| 700 | 1 | |a Worrall, Daniel P |e verfasserin |4 aut | |
| 700 | 1 | |a Hall, Kathryn E |e verfasserin |4 aut | |
| 700 | 1 | |a Ghebremichael, Musie |e verfasserin |4 aut | |
| 700 | 1 | |a Walker, Bruce D |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Jonathan Z |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Xu G |e verfasserin |4 aut | |
| 700 | 1 | |a Mathis, Diane |e verfasserin |4 aut | |
| 700 | 1 | |a Benoist, Christophe |e verfasserin |4 aut | |
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