<p>While the inhibitory receptor <a href="https://www.ncbi.nlm.nih.gov/gene/2213">FcγRIIB </a>has been shown to be upregulated on activated <a href="https://www.ncbi.nlm.nih.gov/gene/925">CD8</a>+ T cells in both mice and humans, its impact on T cell fate during infection has not been fully elucidated. We identified an increase in FcγRIIB-expressing CD8+ T cells in COVID patients relative to healthy controls, and in mouse models of viral infection. Despite its well-known role as an Fc receptor, FcγRIIB also ligates the immunosuppressive cytokine <a href="https://www.ncbi.nlm.nih.gov/gene/10875">Fgl2</a>, resulting in CD8+ T cell apoptosis. Both chronic LCMV infection in mice and COVID in humans resulted in a significant increase in plasma Fgl2. Further, plasma Fgl2 was directly proportional to CD8+ T cell lymphopenia in COVID patients. To further understand the association of Fgl2 and CD8+ T cell lymphopenia following COVID infection, we assessed the transcriptomic profiles of PBMCs with high (≥ 9.153 ng/ml) vs low (defined as &#x3C; 9.153 ng/ml) plasma Fgl2, the median of Fgl2 concentration found in patients. Samples were derived from patients who tested positive for SARS-CoV-2 and were hospitalized at Emory University Hospital between May and July of 2020. RNA-Seq analysis demonstrated that high vs low plasma levels of Fgl2 resulted in perturbations in the transcriptomic profile, with upregulation in pathways associated with erythrocyte metabolism in individuals with high Fgl2. Fgl2 has been shown as an inflammatory mediator underlying coagulopathy, and the increased observance of genes associated with erythrocytes could indicate increased thrombosis in these patients. </p>

Fgl2 Regulates FcγRIIB+ CD8+ T Cell Responses during Infection

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