Functional monocytic myeloid-derived suppressor cells increase in blood but not airways and predict COVID-19 severity.
Identifieur interne : 000073 ( Main/Exploration ); précédent : 000072; suivant : 000074Functional monocytic myeloid-derived suppressor cells increase in blood but not airways and predict COVID-19 severity.
Auteurs : Sara Falck-Jones [Suède] ; Sindhu Vangeti [Suède] ; Meng Yu [Suède] ; Ryan Falck-Jones [Suède] ; Alberto Cagigi [Suède] ; Isabella Badolati [Suède] ; Björn Österberg [Suède] ; Maximilian Julius Lautenbach [Suède] ; Eric Ahlberg [Suède] ; Ang Lin [Suède] ; Rico Lepzien [Suède] ; Inga Szurgot [Suède] ; Klara Lenart [Suède] ; Fredrika Hellgren [Suède] ; Holden T. Maecker [États-Unis] ; Jörgen S Lde [Suède] ; Jan Albert [Suède] ; Niclas Johansson [Suède] ; Max Bell [Suède] ; Karin Lore [Suède] ; Anna F Rnert [Suède] ; Anna Smed-Sörensen [Suède]Source :
- The Journal of clinical investigation [ 1558-8238 ] ; 2021.
Abstract
The immunopathology of COVID-19 remains enigmatic, exhibiting immunodysregulation and T cell lymphopenia. Monocytic myeloid-derived suppressor cells (M-MDSC) are T cell suppressors that expand in inflammatory conditions, but their role in acute respiratory infections remains unclear. We studied blood and airways of COVID-19 patients across disease severity at multiple timepoints. M-MDSC frequencies were elevated in blood but not in nasopharyngeal or endotracheal aspirates of COVID-19 patients compared to controls. M-MDSCs isolated from COVID-19 patients suppressed T cell proliferation and IFNg production partly via an arginase-1 (Arg-1) dependent mechanism. Furthermore, patients showed increased Arg-1 and IL-6 plasma levels. COVID-19 patients had fewer T cells, and displayed downregulated expression of the CD3ζ chain. Ordinal regression showed that early M-MDSC frequency predicted subsequent disease severity. In conclusion, M-MDSCs expand in blood of COVID-19 patients, suppress T cells and strongly associate with disease severity, suggesting a role for M-MDSCs in the dysregulated COVID-19 immune response.
DOI: 10.1172/JCI144734
PubMed: 33492309
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Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna</wicri:regionArea><wicri:noRegion>Solna</wicri:noRegion></affiliation></author><author><name sortKey="Lenart, Klara" sort="Lenart, Klara" uniqKey="Lenart K" first="Klara" last="Lenart">Klara Lenart</name><affiliation wicri:level="1"><nlm:affiliation>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna</wicri:regionArea><wicri:noRegion>Solna</wicri:noRegion></affiliation></author><author><name sortKey="Hellgren, Fredrika" sort="Hellgren, Fredrika" uniqKey="Hellgren F" first="Fredrika" 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sortKey="Albert, Jan" sort="Albert, Jan" uniqKey="Albert J" first="Jan" last="Albert">Jan Albert</name><affiliation wicri:level="3"><nlm:affiliation>Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Johansson, Niclas" sort="Johansson, Niclas" uniqKey="Johansson N" first="Niclas" last="Johansson">Niclas Johansson</name><affiliation wicri:level="3"><nlm:affiliation>Division of Infectious Diseases, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Division of Infectious Diseases, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Bell, Max" sort="Bell, Max" uniqKey="Bell M" first="Max" last="Bell">Max Bell</name><affiliation wicri:level="1"><nlm:affiliation>Department of Physiology and Pharmacology, Karolinska Insitutet, Solna, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Physiology and Pharmacology, Karolinska Insitutet, Solna</wicri:regionArea><wicri:noRegion>Solna</wicri:noRegion></affiliation></author><author><name sortKey="Lore, Karin" sort="Lore, Karin" uniqKey="Lore K" first="Karin" last="Lore">Karin Lore</name><affiliation wicri:level="1"><nlm:affiliation>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna</wicri:regionArea><wicri:noRegion>Solna</wicri:noRegion></affiliation></author><author><name sortKey="F Rnert, Anna" sort="F Rnert, Anna" uniqKey="F Rnert A" first="Anna" last="F Rnert">Anna F Rnert</name><affiliation wicri:level="3"><nlm:affiliation>Division of Infectious Diseases, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Division of Infectious Diseases, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Smed Sorensen, Anna" sort="Smed Sorensen, Anna" uniqKey="Smed Sorensen A" first="Anna" last="Smed-Sörensen">Anna Smed-Sörensen</name><affiliation wicri:level="1"><nlm:affiliation>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna</wicri:regionArea><wicri:noRegion>Solna</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2021">2021</date><idno type="RBID">pubmed:33492309</idno><idno type="pmid">33492309</idno><idno type="doi">10.1172/JCI144734</idno><idno type="wicri:Area/Main/Corpus">000013</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000013</idno><idno type="wicri:Area/Main/Curation">000013</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000013</idno><idno type="wicri:Area/Main/Exploration">000013</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Functional monocytic myeloid-derived suppressor cells increase in blood but not airways and predict COVID-19 severity.</title><author><name sortKey="Falck Jones, Sara" sort="Falck Jones, Sara" uniqKey="Falck Jones S" first="Sara" last="Falck-Jones">Sara Falck-Jones</name><affiliation wicri:level="1"><nlm:affiliation>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna</wicri:regionArea><wicri:noRegion>Solna</wicri:noRegion></affiliation></author><author><name sortKey="Vangeti, Sindhu" sort="Vangeti, Sindhu" uniqKey="Vangeti S" first="Sindhu" last="Vangeti">Sindhu Vangeti</name><affiliation wicri:level="1"><nlm:affiliation>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna</wicri:regionArea><wicri:noRegion>Solna</wicri:noRegion></affiliation></author><author><name sortKey="Yu, Meng" sort="Yu, Meng" uniqKey="Yu M" first="Meng" last="Yu">Meng Yu</name><affiliation wicri:level="1"><nlm:affiliation>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna</wicri:regionArea><wicri:noRegion>Solna</wicri:noRegion></affiliation></author><author><name sortKey="Falck Jones, Ryan" sort="Falck Jones, Ryan" uniqKey="Falck Jones R" first="Ryan" last="Falck-Jones">Ryan Falck-Jones</name><affiliation wicri:level="1"><nlm:affiliation>Department of Physiology and Pharmacology, Karolinska Institutet, Solna, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Physiology and Pharmacology, Karolinska Institutet, Solna</wicri:regionArea><wicri:noRegion>Solna</wicri:noRegion></affiliation></author><author><name sortKey="Cagigi, Alberto" sort="Cagigi, Alberto" uniqKey="Cagigi A" first="Alberto" last="Cagigi">Alberto Cagigi</name><affiliation wicri:level="1"><nlm:affiliation>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna</wicri:regionArea><wicri:noRegion>Solna</wicri:noRegion></affiliation></author><author><name sortKey="Badolati, Isabella" sort="Badolati, Isabella" uniqKey="Badolati I" first="Isabella" last="Badolati">Isabella Badolati</name><affiliation wicri:level="1"><nlm:affiliation>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna</wicri:regionArea><wicri:noRegion>Solna</wicri:noRegion></affiliation></author><author><name sortKey="Osterberg, Bjorn" sort="Osterberg, Bjorn" uniqKey="Osterberg B" first="Björn" last="Österberg">Björn Österberg</name><affiliation wicri:level="1"><nlm:affiliation>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna</wicri:regionArea><wicri:noRegion>Solna</wicri:noRegion></affiliation></author><author><name sortKey="Lautenbach, Maximilian Julius" sort="Lautenbach, Maximilian Julius" uniqKey="Lautenbach M" first="Maximilian Julius" last="Lautenbach">Maximilian Julius Lautenbach</name><affiliation wicri:level="1"><nlm:affiliation>Division of Infectious Diseases, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Insitutet, Solna, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Division of Infectious Diseases, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Insitutet, Solna</wicri:regionArea><wicri:noRegion>Solna</wicri:noRegion></affiliation></author><author><name sortKey="Ahlberg, Eric" sort="Ahlberg, Eric" uniqKey="Ahlberg E" first="Eric" last="Ahlberg">Eric Ahlberg</name><affiliation wicri:level="1"><nlm:affiliation>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna</wicri:regionArea><wicri:noRegion>Solna</wicri:noRegion></affiliation></author><author><name sortKey="Lin, Ang" sort="Lin, Ang" uniqKey="Lin A" first="Ang" last="Lin">Ang Lin</name><affiliation wicri:level="1"><nlm:affiliation>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna</wicri:regionArea><wicri:noRegion>Solna</wicri:noRegion></affiliation></author><author><name sortKey="Lepzien, Rico" sort="Lepzien, Rico" uniqKey="Lepzien R" first="Rico" last="Lepzien">Rico Lepzien</name><affiliation wicri:level="1"><nlm:affiliation>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna</wicri:regionArea><wicri:noRegion>Solna</wicri:noRegion></affiliation></author><author><name sortKey="Szurgot, Inga" sort="Szurgot, Inga" uniqKey="Szurgot I" first="Inga" last="Szurgot">Inga Szurgot</name><affiliation wicri:level="1"><nlm:affiliation>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna</wicri:regionArea><wicri:noRegion>Solna</wicri:noRegion></affiliation></author><author><name sortKey="Lenart, Klara" sort="Lenart, Klara" uniqKey="Lenart K" first="Klara" last="Lenart">Klara Lenart</name><affiliation wicri:level="1"><nlm:affiliation>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna</wicri:regionArea><wicri:noRegion>Solna</wicri:noRegion></affiliation></author><author><name sortKey="Hellgren, Fredrika" sort="Hellgren, Fredrika" uniqKey="Hellgren F" first="Fredrika" last="Hellgren">Fredrika Hellgren</name><affiliation wicri:level="1"><nlm:affiliation>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna</wicri:regionArea><wicri:noRegion>Solna</wicri:noRegion></affiliation></author><author><name sortKey="Maecker, Holden T" sort="Maecker, Holden T" uniqKey="Maecker H" first="Holden T" last="Maecker">Holden T. Maecker</name><affiliation wicri:level="3"><nlm:affiliation>Microbiology & Immunology, Stanford University School of Medicine, Stanford, United States of America.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Microbiology & Immunology, Stanford University School of Medicine, Stanford</wicri:regionArea><placeName><settlement type="city">Stanford (Californie)</settlement><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="S Lde, Jorgen" sort="S Lde, Jorgen" uniqKey="S Lde J" first="Jörgen" last="S Lde">Jörgen S Lde</name><affiliation wicri:level="3"><nlm:affiliation>Health Care Services Stockholm County, Stockholm, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Health Care Services Stockholm County, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Albert, Jan" sort="Albert, Jan" uniqKey="Albert J" first="Jan" last="Albert">Jan Albert</name><affiliation wicri:level="3"><nlm:affiliation>Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Johansson, Niclas" sort="Johansson, Niclas" uniqKey="Johansson N" first="Niclas" last="Johansson">Niclas Johansson</name><affiliation wicri:level="3"><nlm:affiliation>Division of Infectious Diseases, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Division of Infectious Diseases, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Bell, Max" sort="Bell, Max" uniqKey="Bell M" first="Max" last="Bell">Max Bell</name><affiliation wicri:level="1"><nlm:affiliation>Department of Physiology and Pharmacology, Karolinska Insitutet, Solna, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Physiology and Pharmacology, Karolinska Insitutet, Solna</wicri:regionArea><wicri:noRegion>Solna</wicri:noRegion></affiliation></author><author><name sortKey="Lore, Karin" sort="Lore, Karin" uniqKey="Lore K" first="Karin" last="Lore">Karin Lore</name><affiliation wicri:level="1"><nlm:affiliation>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna</wicri:regionArea><wicri:noRegion>Solna</wicri:noRegion></affiliation></author><author><name sortKey="F Rnert, Anna" sort="F Rnert, Anna" uniqKey="F Rnert A" first="Anna" last="F Rnert">Anna F Rnert</name><affiliation wicri:level="3"><nlm:affiliation>Division of Infectious Diseases, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Division of Infectious Diseases, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Smed Sorensen, Anna" sort="Smed Sorensen, Anna" uniqKey="Smed Sorensen A" first="Anna" last="Smed-Sörensen">Anna Smed-Sörensen</name><affiliation wicri:level="1"><nlm:affiliation>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna</wicri:regionArea><wicri:noRegion>Solna</wicri:noRegion></affiliation></author></analytic><series><title level="j">The Journal of clinical investigation</title><idno type="eISSN">1558-8238</idno><imprint><date when="2021" type="published">2021</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The immunopathology of COVID-19 remains enigmatic, exhibiting immunodysregulation and T cell lymphopenia. Monocytic myeloid-derived suppressor cells (M-MDSC) are T cell suppressors that expand in inflammatory conditions, but their role in acute respiratory infections remains unclear. We studied blood and airways of COVID-19 patients across disease severity at multiple timepoints. M-MDSC frequencies were elevated in blood but not in nasopharyngeal or endotracheal aspirates of COVID-19 patients compared to controls. M-MDSCs isolated from COVID-19 patients suppressed T cell proliferation and IFNg production partly via an arginase-1 (Arg-1) dependent mechanism. Furthermore, patients showed increased Arg-1 and IL-6 plasma levels. COVID-19 patients had fewer T cells, and displayed downregulated expression of the CD3ζ chain. Ordinal regression showed that early M-MDSC frequency predicted subsequent disease severity. In conclusion, M-MDSCs expand in blood of COVID-19 patients, suppress T cells and strongly associate with disease severity, suggesting a role for M-MDSCs in the dysregulated COVID-19 immune response.</div></front></TEI><pubmed><MedlineCitation Status="Publisher" Owner="NLM"><PMID Version="1">33492309</PMID><DateRevised><Year>2021</Year><Month>01</Month><Day>25</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1558-8238</ISSN><JournalIssue CitedMedium="Internet"><PubDate><Year>2021</Year><Month>Jan</Month><Day>25</Day></PubDate></JournalIssue><Title>The Journal of clinical investigation</Title><ISOAbbreviation>J Clin Invest</ISOAbbreviation></Journal><ArticleTitle>Functional monocytic myeloid-derived suppressor cells increase in blood but not airways and predict COVID-19 severity.</ArticleTitle><ELocationID EIdType="doi" ValidYN="Y">10.1172/JCI144734</ELocationID><ELocationID EIdType="pii" ValidYN="Y">144734</ELocationID><Abstract><AbstractText>The immunopathology of COVID-19 remains enigmatic, exhibiting immunodysregulation and T cell lymphopenia. Monocytic myeloid-derived suppressor cells (M-MDSC) are T cell suppressors that expand in inflammatory conditions, but their role in acute respiratory infections remains unclear. We studied blood and airways of COVID-19 patients across disease severity at multiple timepoints. M-MDSC frequencies were elevated in blood but not in nasopharyngeal or endotracheal aspirates of COVID-19 patients compared to controls. M-MDSCs isolated from COVID-19 patients suppressed T cell proliferation and IFNg production partly via an arginase-1 (Arg-1) dependent mechanism. Furthermore, patients showed increased Arg-1 and IL-6 plasma levels. COVID-19 patients had fewer T cells, and displayed downregulated expression of the CD3ζ chain. Ordinal regression showed that early M-MDSC frequency predicted subsequent disease severity. In conclusion, M-MDSCs expand in blood of COVID-19 patients, suppress T cells and strongly associate with disease severity, suggesting a role for M-MDSCs in the dysregulated COVID-19 immune response.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Falck-Jones</LastName><ForeName>Sara</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Vangeti</LastName><ForeName>Sindhu</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yu</LastName><ForeName>Meng</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Falck-Jones</LastName><ForeName>Ryan</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Department of Physiology and Pharmacology, Karolinska Institutet, Solna, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cagigi</LastName><ForeName>Alberto</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Badolati</LastName><ForeName>Isabella</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Österberg</LastName><ForeName>Björn</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lautenbach</LastName><ForeName>Maximilian Julius</ForeName><Initials>MJ</Initials><AffiliationInfo><Affiliation>Division of Infectious Diseases, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Insitutet, Solna, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ahlberg</LastName><ForeName>Eric</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lin</LastName><ForeName>Ang</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lepzien</LastName><ForeName>Rico</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Szurgot</LastName><ForeName>Inga</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lenart</LastName><ForeName>Klara</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hellgren</LastName><ForeName>Fredrika</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Maecker</LastName><ForeName>Holden T</ForeName><Initials>HT</Initials><AffiliationInfo><Affiliation>Microbiology & Immunology, Stanford University School of Medicine, Stanford, United States of America.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sälde</LastName><ForeName>Jörgen</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Health Care Services Stockholm County, Stockholm, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Albert</LastName><ForeName>Jan</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Johansson</LastName><ForeName>Niclas</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Division of Infectious Diseases, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bell</LastName><ForeName>Max</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Physiology and Pharmacology, Karolinska Insitutet, Solna, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lore</LastName><ForeName>Karin</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Färnert</LastName><ForeName>Anna</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Division of Infectious Diseases, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Smed-Sörensen</LastName><ForeName>Anna</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Solna, Sweden.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2021</Year><Month>01</Month><Day>25</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Clin Invest</MedlineTA><NlmUniqueID>7802877</NlmUniqueID><ISSNLinking>0021-9738</ISSNLinking></MedlineJournalInfo><CitationSubset>AIM</CitationSubset><CitationSubset>IM</CitationSubset><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">COVID-19</Keyword><Keyword MajorTopicYN="N">Immunology</Keyword><Keyword MajorTopicYN="N">Innate immunity</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2021</Year><Month>1</Month><Day>25</Day><Hour>12</Hour><Minute>12</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2021</Year><Month>1</Month><Day>26</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2021</Year><Month>1</Month><Day>26</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>aheadofprint</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">33492309</ArticleId><ArticleId IdType="pii">144734</ArticleId><ArticleId IdType="doi">10.1172/JCI144734</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Suède</li><li>États-Unis</li></country><region><li>Californie</li><li>Svealand</li></region><settlement><li>Stanford (Californie)</li><li>Stockholm</li></settlement></list><tree><country name="Suède"><noRegion><name sortKey="Falck Jones, Sara" sort="Falck Jones, Sara" uniqKey="Falck Jones S" first="Sara" last="Falck-Jones">Sara Falck-Jones</name></noRegion><name sortKey="Ahlberg, Eric" sort="Ahlberg, Eric" uniqKey="Ahlberg E" first="Eric" last="Ahlberg">Eric Ahlberg</name><name sortKey="Albert, Jan" sort="Albert, Jan" uniqKey="Albert J" first="Jan" last="Albert">Jan Albert</name><name sortKey="Badolati, Isabella" sort="Badolati, Isabella" uniqKey="Badolati I" first="Isabella" last="Badolati">Isabella Badolati</name><name sortKey="Bell, Max" sort="Bell, Max" uniqKey="Bell M" first="Max" last="Bell">Max Bell</name><name sortKey="Cagigi, Alberto" sort="Cagigi, Alberto" uniqKey="Cagigi A" first="Alberto" last="Cagigi">Alberto Cagigi</name><name sortKey="F Rnert, Anna" sort="F Rnert, Anna" uniqKey="F Rnert A" first="Anna" last="F Rnert">Anna F Rnert</name><name sortKey="Falck Jones, Ryan" sort="Falck Jones, Ryan" uniqKey="Falck Jones R" first="Ryan" last="Falck-Jones">Ryan Falck-Jones</name><name sortKey="Hellgren, Fredrika" sort="Hellgren, Fredrika" uniqKey="Hellgren F" first="Fredrika" last="Hellgren">Fredrika Hellgren</name><name sortKey="Johansson, Niclas" sort="Johansson, Niclas" uniqKey="Johansson N" first="Niclas" last="Johansson">Niclas Johansson</name><name sortKey="Lautenbach, Maximilian Julius" sort="Lautenbach, Maximilian Julius" uniqKey="Lautenbach M" first="Maximilian Julius" last="Lautenbach">Maximilian Julius Lautenbach</name><name sortKey="Lenart, Klara" sort="Lenart, Klara" uniqKey="Lenart K" first="Klara" last="Lenart">Klara Lenart</name><name sortKey="Lepzien, Rico" sort="Lepzien, Rico" uniqKey="Lepzien R" first="Rico" last="Lepzien">Rico Lepzien</name><name sortKey="Lin, Ang" sort="Lin, Ang" uniqKey="Lin A" first="Ang" last="Lin">Ang Lin</name><name sortKey="Lore, Karin" sort="Lore, Karin" uniqKey="Lore K" first="Karin" last="Lore">Karin Lore</name><name sortKey="Osterberg, Bjorn" sort="Osterberg, Bjorn" uniqKey="Osterberg B" first="Björn" last="Österberg">Björn Österberg</name><name sortKey="S Lde, Jorgen" sort="S Lde, Jorgen" uniqKey="S Lde J" first="Jörgen" last="S Lde">Jörgen S Lde</name><name sortKey="Smed Sorensen, Anna" sort="Smed Sorensen, Anna" uniqKey="Smed Sorensen A" first="Anna" last="Smed-Sörensen">Anna Smed-Sörensen</name><name sortKey="Szurgot, Inga" sort="Szurgot, Inga" uniqKey="Szurgot I" first="Inga" last="Szurgot">Inga Szurgot</name><name sortKey="Vangeti, Sindhu" sort="Vangeti, Sindhu" uniqKey="Vangeti S" first="Sindhu" last="Vangeti">Sindhu Vangeti</name><name sortKey="Yu, Meng" sort="Yu, Meng" uniqKey="Yu M" first="Meng" last="Yu">Meng Yu</name></country><country name="États-Unis"><region name="Californie"><name sortKey="Maecker, Holden T" sort="Maecker, Holden T" uniqKey="Maecker H" first="Holden T" last="Maecker">Holden T. 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