ArticleThe Journal of clinical investigation2024
IL-6-mediated endothelial injury impairs antiviral humoral immunity after bone marrow transplantation.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 8 citations in OpenAlex.
- Human Cytomegalovirus Infection in Haematopoietic Stem Cell Transplant Recipients and CAR T Cell Recipients - PART 1: Risk Factors, Clinical Impact and Immune Response.Reviews in medical virology · 2026Review
- Validation of risk stratification and novel prognostic biomarkers in asian adult HSCT recipients with TA-TMA: A multicenter real-world study.Bone marrow transplantation · 2026Article
- Nomogram-based prediction model for tocilizumab-induced leukopenia in adults using FAERS and PMDA data.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas · 2026Observational
- Innovation in active and passive immunisation of people who are immunocompromised: a call to action.The Lancet. Infectious diseases · 2026Review
- Study on the prediction of prognosis of patients with acute liver failure treated with artificial liver by serum NLR and IL-6 levels.Journal of medical biochemistry · 2025Article
- Interleukin-6: Molecular Mechanisms and Therapeutic Perspectives in Atrial Fibrillation.Current medical science · 2025Review
- High level serum IL-6 predicts occurrence of TA-TMA.Bone marrow transplantation · 2025Article
- The intersection of influenza infection and autoimmunity.Frontiers in immunology · 2025Review
- Tocilizumab-Based Treatment of Microvascular Inflammation in Kidney Transplant Recipients: A Retrospective Study.Transplant international : official journal of the European Society for Organ Transplantation · 2025Article
Corrections and comments
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Authors and funding
31 authors at 7 institutions in 3 countries.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.