COVID-19 and RA share an SPP1 myeloid pathway that drives PD-L1+ neutrophils and CD14+ monocytes

Abstract

Severe COVID-19 and active Rheumatoid Arthritis share tissue macrophage clusters with a hallmark pro-inflammatory mediator osteopontin (SPP1) that activates PD-L1 pos neutrophils and classical monocytes, and persist into post-COVID-19 phase.

COVID-19 and Rheumatoid Arthritis Crosstalk: Emerging Association, Therapeutic Options and Challenges

“…During SARS-CoV-2 infection, the number of FABP4-expressing (FABP4 positive ) alveolar macrophages is substantially reduced, and thus gas exchange is compromised [ 52 ] ( Figure 4 ). Bronchoalveolar lavage fluids from COVID-19 patients exhibit more distinct types of macrophages than resident macrophages present in healthy alveoli [ 53 ]. The alveolar tissue of COVID-19 patients abundantly presents two distinct macrophage clusters expressing ficolin-1 (FCN1), which can be differentiated by their relative expression of secreted phosphoprotein 1/osteopontin (SPP1) [ 53 ].…”

“…Bronchoalveolar lavage fluids from COVID-19 patients exhibit more distinct types of macrophages than resident macrophages present in healthy alveoli [ 53 ]. The alveolar tissue of COVID-19 patients abundantly presents two distinct macrophage clusters expressing ficolin-1 (FCN1), which can be differentiated by their relative expression of secreted phosphoprotein 1/osteopontin (SPP1) [ 53 ]. These are categorized as only FCN expressing macrophages (FCN positive ) and macrophages that express both FCN and SPP1 (FCN positive SPP1 positive ).…”

“…As compared to healthy joints, synovial tissue of RA patients additionally represents two distinct types of macrophage clusters: one is highly expressing CD48 and S100A12 (S100 calcium-binding protein A12/calgranulin C), while another is expressing both CD48 and SPP1 ( Figure 4 ). Both CD48 high S100A12 positive and CD48 positive SPP1 positive macrophage clusters have been revealed to be associated with RA pathogenesis via producing pro-inflammatory mediators such as IL-1β, IL-6, TNF-α, MMPs, and chemokines and inducing pathogenesis to the adjacent stromal tissue [ 53 ]. FCN positive and FCN positive SPP1 positive macrophages in bronchoalveolar lavage fluids from COVID-19 patients share a transcriptional homology with pathogenic CD48 high S100A12 positive and CD48 positive SPP1 positive macrophage clusters in the synovial tissue of RA patients ( Figure 4 ) [ 53 ].…”

“…Both CD48 high S100A12 positive and CD48 positive SPP1 positive macrophage clusters have been revealed to be associated with RA pathogenesis via producing pro-inflammatory mediators such as IL-1β, IL-6, TNF-α, MMPs, and chemokines and inducing pathogenesis to the adjacent stromal tissue [ 53 ]. FCN positive and FCN positive SPP1 positive macrophages in bronchoalveolar lavage fluids from COVID-19 patients share a transcriptional homology with pathogenic CD48 high S100A12 positive and CD48 positive SPP1 positive macrophage clusters in the synovial tissue of RA patients ( Figure 4 ) [ 53 ]. In addition, both share similar functional characteristics in the respective tissues [ 53 ].…”

“…FCN positive and FCN positive SPP1 positive macrophages in bronchoalveolar lavage fluids from COVID-19 patients share a transcriptional homology with pathogenic CD48 high S100A12 positive and CD48 positive SPP1 positive macrophage clusters in the synovial tissue of RA patients ( Figure 4 ) [ 53 ]. In addition, both share similar functional characteristics in the respective tissues [ 53 ]. Similarly, FABP4 positive alveolar macrophages in the bronchoalveolar lavage fluids from healthy individuals share transcriptional and functional homology with TREM2 expressing synovial macrophages in healthy joints ( Figure 4 ) [ 53 ].…”