Fgl2 regulates FcγRIIB+CD8+ T cell responses during infection

• DOI: 10.1172/jci.insight.186259
• Publication Date: 2025-04-07T18:04:17Z
• Authors: Anna B. Morris; Max W. Adelman; Kelsey B. Bennion; Catherine D. Mart...; Kem-Maria McCook; Michael H. Woodworth; Charles R. Langelier; Nadine Rouphael; Christopher D. Sc...; Cheryl L. Maier; Colleen S. Kraft; Mandy L. Ford

While the inhibitory receptor FcγRIIB has been shown to be upregulated on activated CD8+ T cells in both mice and humans, its effect cell fate during infection not fully elucidated. We identified an increase FcγRIIB-expressing patients with COVID-19 relative healthy controls as well mouse models of viral infection. Despite well-known role Fc receptor, also ligates immunosuppressive cytokine Fgl2, resulting apoptosis. Both chronic LCMV humans resulted a significant plasma Fgl2. Transfer into Fgl2-replete, but Fgl2-devoid, environment elimination FcγRIIB+, FcγRIIB-, cells. Similarly, Fgl2 was directly proportional lymphopenia COVID-19. RNA-Seq analysis demonstrated that produced by murine virus-specific cells, elicited versus acute from controls. In summary, production underpinned FcγRIIB-mediated loss immunity humans.