Novel Link Between Myeloid-Specific Adenosine Deaminase 2 and CXCL10-CXCR3 Axis in Infectious ARDS

TL;DR

This study finds a new connection between the enzyme ADA2 and the CXCL10-CXCR3 pathway in severe lung disease caused by SARS-CoV-2.

Contribution

The novel link between ADA2 and the CXCL10-CXCR3 axis in infectious ARDS is identified using spatial transcriptomics and single-cell RNAseq data.

Findings

ADA2 is highly expressed by inflammatory CD14+CD16+ monocytes in lungs affected by COVID-19.

ADA2 is associated with profibrotic genes and key features of ARDS pathophysiology.

The study links ADA2 with hypoxia and CXCR3 monocyte infiltration in ARDS.

Abstract

Acute respiratory distress syndrome (ARDS) is a severe complication of lung injury characterized by hyperinflammation and fibrosis. Here, we show a significant association between the monocyte-derived enzyme adenosine deaminase 2 (ADA2) and SARS-CoV-2 induced ARDS. We note an interesting link between ADA2 and the chemokine CXCL10 and its receptor CXCR3. By using published datasets of spatial transcriptomics and single-cell RNAseq, we show that ADA2 is highly expressed by inflammatory CD14+CD16+ monocytes, along with profibrotic genes, in lungs affected by COVID-19. This study reveals important associations between key pathophysiological features of ARDS, linking hypoxia, infiltrative CXCR3 monocytes, and a monocyte-derived exoenzyme ADA2.

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