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G6PD deficiency shifts polarization of monocytes/macrophages towards a proinflammatory and profibrotic phenotype

Cellular & Molecular Immunology volume 18, pages 770–772 (2021)Cite this article

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Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common inherited trait and affects ~7% of the global population. The G6PD A− variant (class III), which has mild-to-moderate residual enzymatic activity (10–60%), is present in 11–14% of African American (AA) individuals. Meta-analysis and epidemiological studies from different countries have shown that individuals with G6PD deficiency have an increased risk of developing diabetes and cardiovascular disease.1,2 G6PD deficiency increases the risk of elevated systolic blood pressure and the incidence of CVD among populations in USA, the Mediterranean region, and China.1,3,4 G6PD deficiency is also associated with fibrosis, autoimmune diseases, metabolic disorders, and sporadic Alzheimer’s disease, indicating that the clinical risks associated with G6PD deficiency are likely to be underestimated.

Differentiation of monocytes to resident macrophages occurs when monocytes enter the tissue and are under the control of local environmental cues. Monocytes and macrophages play vital roles in the innate immune defense against invading pathogens and support adaptive immunity, tumor surveillance, and cardiovascular homeostasis.5 Two extreme states of activated macrophages are M1-like macrophages (in response to inflammatory stimuli such as LPS and IFNγ) and M2-like macrophages (in response to cytokines such as IL4 and IL-13).5 However, the contribution of G6PD deficiency to monocyte/macrophage polarization is currently unknown.

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Acknowledgements

The Malcolm W. Feist Cardiovascular Research Fellowship provided support for this study to RP and the Endowed Chair in Diabetes to SKJ from the Center for Cardiovascular Diseases and Sciences, LSUHSC-Shreveport. SKJ also received support from grants from the National Institutes of Health/National Center for Complementary and Integrative Health (RO1 AT007442, 2013-16). We thank Ms Paula Polk, Manager, and Dr Wiola Luszczek, Research Specialist, at the Research Core Facility at LSUHSC-Shreveport, for their expert technical assistance. We also thank Mr William E. McLean and Mr Christopher M. Stevens for lab assistance. The authors thank Ms Georgia Morgan for excellent editing.

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  1. Department of Pediatrics and Center for Cardiovascular Diseases and Sciences, Louisiana State University Health Sciences Center-Shreveport, 1501 Kings Highway, Shreveport, LA, 71130, USA

    Rajesh Parsanathan & Sushil K. Jain

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  1. Rajesh Parsanathan
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  2. Sushil K. Jain
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RP and SKJ conceived and designed the experiment and analyzed the data; RP performed the experiments and wrote the original draft; RP and SKJ reviewed and approved the final manuscript.

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Correspondence to Sushil K. Jain.

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Parsanathan, R., Jain, S.K. G6PD deficiency shifts polarization of monocytes/macrophages towards a proinflammatory and profibrotic phenotype. Cell Mol Immunol 18, 770–772 (2021). https://doi.org/10.1038/s41423-020-0428-5

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