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Published on: June 2, 2022
Novel Link Between Myeloid-Specific Adenosine Deaminase 2 and CXCL10-CXCR3 Axis in Infectious ARDS
Shilpa Tiwari-Heckler1, Yered Pita-Juarez2, Lisa Vierbaum1
1Department of Gastroenterology, Infectiology and Toxicology, University Hospital Heidelberg, 69120 Heidelberg, Germany.
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.
Insights
The enzyme adenosine deaminase 2 (ADA2) is linked to severe COVID-19 lung injury, known as acute respiratory distress syndrome (ARDS). This study finds ADA2 expressed by inflammatory monocytes in ARDS lungs, connecting hypoxia and fibrosis.
Area of Science:
- Immunology
- Pulmonology
- Molecular Biology
Background:
- Acute respiratory distress syndrome (ARDS) is a severe lung injury complication.
- ARDS involves hyperinflammation and fibrosis.
- SARS-CoV-2 infection can cause ARDS.
Purpose of the Study:
- To investigate the association between adenosine deaminase 2 (ADA2) and SARS-CoV-2 induced ARDS.
- To explore the link between ADA2, chemokines (CXCL10/CXCR3), and ARDS pathophysiology.
Main Methods:
- Analysis of published spatial transcriptomics and single-cell RNA sequencing datasets.
- Examination of gene expression in lung tissue from COVID-19 patients.
Main Results:
- A significant association was found between ADA2 and SARS-CoV-2 induced ARDS.
- ADA2 is highly expressed by inflammatory CD14+CD16+ monocytes in COVID-19 affected lungs.
- Profibrotic genes were co-expressed with ADA2 in these monocytes.
Conclusions:
- ADA2 is a key enzyme associated with ARDS pathogenesis in COVID-19.
- The study links hypoxia, CXCR3+ monocyte infiltration, and ADA2 in ARDS.
- ADA2 represents a potential therapeutic target in ARDS.
