CITE-seq analysis reveals human cytomegalovirus and diabetes-associated adaptive NK cell alterations in cardiovascular disease.

Armstrong, S. S.; Chen, D. G.; Kumar, S.; Heath, J. R.; Feinstein, M.; Greenland, J. R.; Calabrese, D. R.; Lanier, L. L.; Ley, K.; Shemesh, A.

doi:10.1101/2024.03.22.581997

bioRxiv · 10.1101/2024.03.22.581997

CITE-seq analysis reveals human cytomegalovirus and diabetes-associated adaptive NK cell alterations in cardiovascular disease.

Armstrong, S. S.·Chen, D. G.·Kumar, S.·Heath, J. R.·Feinstein, M.·Greenland, J. R.·Calabrese, D. R.·Lanier, L. L.·Ley, K.·Shemesh, A.

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Abstract

Coronary artery disease (CAD) is a leading cause of mortality worldwide with Diabetes and human cyto-megalovirus (HCMV) infection as risk factors. CADs influence on human NK cells is not well characterized. CITE-seq analysis of a CAD cohort of 61 patients revealed distinctly higher NK cell SPON2 expression and lower IFNG expression in severe CAD patients. Interestingly, HCMV+ patients displayed lower SPON2 ex-pression while diabetes status reversed the HCMV effect. Diabetes led to diminished adaptive Fc{varepsilon}RI{gamma}-/low NK cell frequencies and was associated with a higher PBMC IL15/TGFB transcript ratio, while TGFB in-creased in severe CAD. SPON2 expression corresponded to changes in conventional vs. adaptive NK cell frequencies, and SPON2/IFNG ratio decreased in inflamed plaque tissue with an increased adaptive NK cell gene signature and was increased in severe CAD patients. Our results indicate that the SPON2/IFNG ra-tio and adaptive NK cell gene signature associated with stenosis severity or inflammation in CAD.

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Armstrong, S. S., Chen, D. G., Kumar, S., Heath, J. R., Feinstein, M., Greenland, J. R., Calabrese, D. R., Lanier, L. L., Ley, K., Shemesh, A.. 2024-03-26. CITE-seq analysis reveals human cytomegalovirus and diabetes-associated adaptive NK cell alterations in cardiovascular disease.. https://doi.org/10.1101/2024.03.22.581997

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