Editorial: Hypoxia and inflammation: A two-way street

Review Immunology

The hypoxic tissue microenvironment as a driver of mucosal inflammatory resolution

Ian M. Cartwright et al.

Summary: The activation of the resolution response is essential for the resolution of acute inflammatory processes. Hypoxia, particularly in the gastrointestinal tract, plays a key role in promoting the active resolution of inflammation through various mechanisms. Infiltrating immune cells and altered microenvironmental factors also contribute to the resolution of inflammation.

FRONTIERS IN IMMUNOLOGY (2023)

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Article Cell Biology

Metabolic adaptation supports enhanced macrophage efferocytosis in limited-oxygen environments

Ya-Ting Wang et al.

Summary: Research reveals that macrophages exhibit enhanced efferocytosis of apoptotic cells under prolonged physiological hypoxia, characterized by increased internalization and accelerated degradation. This is achieved through the noncanonical pentose phosphate pathway, which promotes NADPH production and ensures phagolysosomal maturation and redox homeostasis. This adaptation supports cell fitness and essential homeostatic functions.

CELL METABOLISM (2023)

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Article Cell Biology

Alterations in CD39/CD73 axis of T cells associated with COVID-19 severity

Gilson P. Dorneles et al.

Summary: This study investigates alterations in purinergic pathways in COVID-19 patients and provides new insights into the immunopathology of the disease. The findings suggest that the purinergic signaling is dysregulated in both mild and severe COVID-19 patients, which may affect immune function. Additionally, increased T-cell apoptosis and decreased purine levels are observed in COVID-19 patients compared to healthy controls.

JOURNAL OF CELLULAR PHYSIOLOGY (2022)

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Article Immunology

Dysfunctional purinergic signaling correlates with disease severity in COVID-19 patients

Anna Julia Pietrobon et al.

Summary: This study investigated the contribution of extracellular nucleotide metabolism to the severity of COVID-19. The researchers found that the gene expression of ectonucleotidases is reduced in COVID-19 patients and is negatively correlated with CRP levels, an inflammatory marker of disease severity. Additionally, COVID-19 patients have higher ATP levels and lower ADO levels in plasma compared to healthy controls. Cell type-specific analysis revealed higher frequencies of CD39+ T cells and lower frequencies of CD4+ and CD8+ expressing CD73 cells in severely ill patients. The study also found that B cells from COVID-19 patients have a reduced ability to hydrolyze ATP into ADP and ADO, and there is impaired expression of ADO receptors and signaling pathway activation in these patients. The presence of ADO in vitro suppressed inflammatory responses in patients' cells. Overall, these findings suggest that alterations in extracellular purine metabolism contribute to immune dysregulation in COVID-19 and ADO could be a therapeutic approach for the disease.

FRONTIERS IN IMMUNOLOGY (2022)

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Review Medicine, Research & Experimental