COVID-19 and RA share an SPP1 myeloid pathway that drives PD-L1+ neutrophils and CD14+ monocytes.
Arthritis, Rheumatoid
/ immunology
B7-H1 Antigen
/ immunology
Bronchoalveolar Lavage Fluid
/ immunology
CD48 Antigen
/ immunology
COVID-19
/ chemically induced
Fatty Acid-Binding Proteins
/ immunology
Humans
Lectins
/ immunology
Lipopolysaccharide Receptors
/ immunology
Lung
/ diagnostic imaging
Macrophages
/ immunology
Membrane Glycoproteins
/ immunology
Monocytes
/ immunology
Neutrophils
/ immunology
Osteopontin
/ blood
Receptor Protein-Tyrosine Kinases
/ metabolism
Receptors, Immunologic
/ immunology
S100A12 Protein
/ immunology
Synovial Membrane
/ immunology
Tomography, X-Ray Computed
Ficolins
Autoimmune diseases
Infectious disease
Inflammation
Macrophages
Journal
JCI insight
ISSN: 2379-3708
Titre abrégé: JCI Insight
Pays: United States
ID NLM: 101676073
Informations de publication
Date de publication:
18 06 2021
18 06 2021
Historique:
received:
04
01
2021
accepted:
02
06
2021
pubmed:
19
6
2021
medline:
21
7
2021
entrez:
18
6
2021
Statut:
epublish
Résumé
We explored the potential link between chronic inflammatory arthritis and COVID-19 pathogenic and resolving macrophage pathways and their role in COVID-19 pathogenesis. We found that bronchoalveolar lavage fluid (BALF) macrophage clusters FCN1+ and FCN1+SPP1+ predominant in severe COVID-19 were transcriptionally related to synovial tissue macrophage (STM) clusters CD48hiS100A12+ and CD48+SPP1+ that drive rheumatoid arthritis (RA) synovitis. BALF macrophage cluster FABP4+ predominant in healthy lung was transcriptionally related to STM cluster TREM2+ that governs resolution of synovitis in RA remission. Plasma concentrations of SPP1 and S100A12 (key products of macrophage clusters shared with active RA) were high in severe COVID-19 and predicted the need for Intensive Care Unit transfer, and they remained high in the post-COVID-19 stage. High plasma levels of SPP1 were unique to severe COVID-19 when compared with other causes of severe pneumonia, and IHC localized SPP1+ macrophages in the alveoli of COVID-19 lung. Investigation into SPP1 mechanisms of action revealed that it drives proinflammatory activation of CD14+ monocytes and development of PD-L1+ neutrophils, both hallmarks of severe COVID-19. In summary, COVID-19 pneumonitis appears driven by similar pathogenic myeloid cell pathways as those in RA, and their mediators such as SPP1 might be an upstream activator of the aberrant innate response in severe COVID-19 and predictive of disease trajectory including post-COVID-19 pathology.
Identifiants
pubmed: 34143756
pii: e147413
doi: 10.1172/jci.insight.147413
pmc: PMC8328085
doi:
pii:
Substances chimiques
B7-H1 Antigen
0
CD14 protein, human
0
CD274 protein, human
0
CD48 Antigen
0
CD48 protein, human
0
FABP4 protein, human
0
Fatty Acid-Binding Proteins
0
Lectins
0
Lipopolysaccharide Receptors
0
Membrane Glycoproteins
0
Receptors, Immunologic
0
S100A12 Protein
0
S100A12 protein, human
0
SPP1 protein, human
0
TREM2 protein, human
0
Osteopontin
106441-73-0
Receptor Protein-Tyrosine Kinases
EC 2.7.10.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/V036998/1
Pays : United Kingdom
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