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J Clin Invest ; 134(7)2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38557487

RESUMEN

Endothelial function and integrity are compromised after allogeneic bone marrow transplantation (BMT), but how this affects immune responses broadly remains unknown. Using a preclinical model of CMV reactivation after BMT, we found compromised antiviral humoral responses induced by IL-6 signaling. IL-6 signaling in T cells maintained Th1 cells, resulting in sustained IFN-γ secretion, which promoted endothelial cell (EC) injury, loss of the neonatal Fc receptor (FcRn) responsible for IgG recycling, and rapid IgG loss. T cell-specific deletion of IL-6R led to persistence of recipient-derived, CMV-specific IgG and inhibited CMV reactivation. Deletion of IFN-γ in donor T cells also eliminated EC injury and FcRn loss. In a phase III clinical trial, blockade of IL-6R with tocilizumab promoted CMV-specific IgG persistence and significantly attenuated early HCMV reactivation. In sum, IL-6 invoked IFN-γ-dependent EC injury and consequent IgG loss, leading to CMV reactivation. Hence, cytokine inhibition represents a logical strategy to prevent endothelial injury, thereby preserving humoral immunity after immunotherapy.


Asunto(s)
Trasplante de Médula Ósea , Infecciones por Citomegalovirus , Inmunidad Humoral , Interleucina-6 , Antivirales , Trasplante de Médula Ósea/efectos adversos , Infecciones por Citomegalovirus/inmunología , Infecciones por Citomegalovirus/metabolismo , Inmunoglobulina G , Interleucina-6/metabolismo , Animales , Ratones
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