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Greenland, J. R.

Publications and source records attributed to Greenland, J. R..

2 recordsLinked to original sources
bioRxiv2021

Natural Killer cell division regulates FcεRIγ expression downstream of mTOR activity

The expansion of human Fc{varepsilon}RI{gamma}-/low (FcR{gamma}-/low) natural killer (NK) cells accrues during viral infections; however, the molecular mechanisms regulating FcR{gamma} expression is not well defined and can have implication for host protection and NK cell immunotherapy. Our analysis of NK cell subsets in lung transplant patients during rapamycin treatment revealed significantly lower FcR{gamma} levels in the NK cell population. Moreover, lower FcR{gamma} levels in healthy donors were associated with low mTORC1/C2 activity and low T-bet expression. Cell division suppression by rapamycin or TGF{beta} suppressed FcR{gamma} upregulation during IL-2 receptor stimulation, whereas promoting NK cell division by co-inhibiting FOXO1 activity restored FcR{gamma} upregulation. These results suggest that the human FcR{gamma}-/low NK cell phenotype is associated with cell division suppression and reduced mTOR activity.

immunology↗
bioRxiv2021

Longitudinal single-cell epitope and RNA-sequencing reveals the immunological impact of type 1 interferon autoantibodies in critical COVID-19

Type I interferon (IFN-I) neutralizing autoantibodies have been found in some critical COVID-19 patients; however, their prevalence and longitudinal dynamics across the disease severity scale, and functional effects on circulating leukocytes remain unknown. Here, in 284 COVID-19 patients, we found IFN-I autoantibodies in 19% of critical, 6% of severe and none of the moderate cases. Longitudinal profiling of over 600,000 peripheral blood mononuclear cells using multiplexed single-cell epitope and transcriptome sequencing from 54 COVID-19 patients, 15 non-COVID-19 patients and 11 non-hospitalized healthy controls, revealed a lack of IFN-I stimulated gene (ISG-I) response in myeloid cells from critical cases, including those producing anti-IFN-I autoantibodies. Moreover, surface protein analysis showed an inverse correlation of the inhibitory receptor LAIR-1 with ISG-I expression response early in the disease course. This aberrant ISG-I response in critical patients with and without IFN-I autoantibodies, supports a unifying model for disease pathogenesis involving ISG-I suppression via convergent mechanisms.

immunology↗