TY - JOUR
T1 - COVID-19 and RA share an SPP1 myeloid pathway that drives PD-L1+ neutrophils and CD14+ monocytes
AU - Macdonald, Lucy
AU - Alivernini, Stefano
AU - Tolusso, Barbara
AU - Elmesmari, Aziza
AU - Somma, Domenico
AU - Perniola, Simone
AU - Paglionico, Annamaria
AU - Petricca, Luca
AU - Bosello, Silvia Laura
AU - Carfì, Angelo
AU - Sali, Michela
AU - Stigliano, Egidio
AU - Cingolani, Antonella
AU - Murri, Rita
AU - Arena, Vincenzo
AU - Fantoni, Massimo
AU - Antonelli, Massimo
AU - Landi, Francesco
AU - Franceschi, Francesco
AU - Sanguinetti, Maurizio
AU - Mcinnes, Iain B.
AU - Mcsharry, Charles
AU - Gasbarrini, Antonio
AU - Otto, Thomas D.
AU - Kurowska-Stolarska, Mariola
AU - Gremese, Elisa
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - Arthritis, Rheumatoid
KW - Autoimmune diseases
KW - B7-H1 Antigen
KW - Bronchoalveolar Lavage Fluid
KW - CD48 Antigen
KW - COVID-19
KW - Fatty Acid-Binding Proteins
KW - Humans
KW - Infectious disease
KW - Inflammation
KW - Lectins
KW - Lipopolysaccharide Receptors
KW - Lung
KW - Macrophages
KW - Membrane Glycoproteins
KW - Monocytes
KW - Neutrophils
KW - Osteopontin
KW - Receptor Protein-Tyrosine Kinases
KW - Receptors, Immunologic
KW - S100A12 Protein
KW - Synovial Membrane
KW - Tomography, X-Ray Computed
KW - Arthritis, Rheumatoid
KW - Autoimmune diseases
KW - B7-H1 Antigen
KW - Bronchoalveolar Lavage Fluid
KW - CD48 Antigen
KW - COVID-19
KW - Fatty Acid-Binding Proteins
KW - Humans
KW - Infectious disease
KW - Inflammation
KW - Lectins
KW - Lipopolysaccharide Receptors
KW - Lung
KW - Macrophages
KW - Membrane Glycoproteins
KW - Monocytes
KW - Neutrophils
KW - Osteopontin
KW - Receptor Protein-Tyrosine Kinases
KW - Receptors, Immunologic
KW - S100A12 Protein
KW - Synovial Membrane
KW - Tomography, X-Ray Computed
UR - http://hdl.handle.net/10807/197056
U2 - 10.1172/jci.insight.147413
DO - 10.1172/jci.insight.147413
M3 - Article
SN - 2379-3708
VL - 6
SP - N/A-N/A
JO - JCI insight
JF - JCI insight
ER -