ArticleBlood2015
Lung parenchyma-derived IL-6 promotes IL-17A-dependent acute lung injury after allogeneic stem cell transplantation.
Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 86 citations in OpenAlex.
- Diagnostic and Prognostic Plasma Biomarkers for Idiopathic Pneumonia Syndrome after Hematopoietic Cell Transplantation.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2018Trial
- Recent advances in the pathophysiology of acute and chronic graft-versus-host disease.International journal of hematology · 2026Review
- Targeted lungScience advances · 2026Article
- Neutrophil-macrophage crosstalk network in acute lung injury: feedback circuits linking cytokine storm and cell death.Frontiers in cellular and infection microbiology · 2026Review
- Th17 cells/IL-17A shape Pasteurella multocida serotype A infection in murine and rabbit models.Veterinary research · 2025Article
- Respiratory transmission potential of severe fever with thrombocytopenia syndrome bunyavirus: evidence from intranasal exposure in a humanized mouse model.Emerging microbes & infections · 2025Article
- Association of donor and recipient single-nucleotide polymorphisms of interleukin-1 gene with outcomes after allogeneic hematopoietic stem cell transplantation in childhood.Journal of cancer research and clinical oncology · 2025Article
- Addressing Knowledge Gaps in the Early Detection of Bronchiolitis Obliterans Syndrome after Hematopoietic Cell Transplantation: An Official American Thoracic Society Research Statement.American journal of respiratory and critical care medicine · 2025Article
- Calcineurin inhibition rescues alloantigen-specific central memory T cell subsets that promote chronic GVHD.The Journal of clinical investigation · 2024Article
- IL-6-mediated endothelial injury impairs antiviral humoral immunity after bone marrow transplantation.The Journal of clinical investigation · 2024Article
- Immune regulation through tryptophan metabolism.Experimental & molecular medicine · 2023Review
- Insight on immune cells in rejection and infection postlung transplant.Immunity, inflammation and disease · 2023Review
- The Development of New Agents for Post-Hematopoietic Stem Cell Transplantation Non-Infectious Complications in Children.Journal of clinical medicine · 2023Review
- Defibrotide modulates pulmonary endothelial cell activation and protects against lung inflammation in pre-clinical models of LPS-induced lung injury and idiopathic pneumonia syndrome.Frontiers in immunology · 2023Article
- Cytokines in Lung Transplantation.Lung · 2022Review
- Reactive granulopoiesis depends on T-cell production of IL-17A and neutropenia-associated alteration of gut microbiota.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- IL-6 Responsiveness of CD4Journal of clinical medicine · 2022Article
- Macrophage-derived IL-6 trans-signalling as a novel target in the pathogenesis of bronchopulmonary dysplasia.The European respiratory journal · 2022Article
- Integrated Network Pharmacology and Experimental Validation Approach to Investigate the Therapeutic Effects of Capsaicin on Lipopolysaccharide-Induced Acute Lung Injury.Mediators of inflammation · 2022Article
- Interleukin-17A and interleukin-22 production by conventional and non-conventional lymphocytes in three different end-stage lung diseases.Clinical & translational immunology · 2022Article
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24 authors at 6 institutions in 2 countries.
Funding
Abstract
Idiopathic pneumonia syndrome (IPS) is a relatively common, frequently fatal clinical entity, characterized by noninfectious acute lung inflammation following allogeneic stem cell transplantation (SCT), the mechanisms of which are unclear. In this study, we demonstrate that immune suppression with cyclosporin after SCT limits T-helper cell (Th) 1 differentiation and interferon-γ secretion by donor T cells, which is critical for inhibiting interleukin (IL)-6 generation from lung parenchyma during an alloimmune response. Thereafter, local IL-6 secretion induces donor alloantigen-specific Th17 cells to preferentially expand within the lung, and blockade of IL-17A or transplantation of grafts lacking the IL-17 receptor prevents disease. Studies using IL-6(-/-) recipients or IL-6 blockade demonstrate that IL-6 is the critical driver of donor Th17 differentiation within the lung. Importantly, IL-6 is also dysregulated in patients undergoing clinical SCT and is present at very high levels in the plasma of patients with IPS compared with SCT recipients without complications. Furthermore, at the time of diagnosis, plasma IL-6 levels were higher in a subset of IPS patients who were nonresponsive to steroids and anti-tumor necrosis factor therapy. In sum, pulmonary-derived IL-6 promotes IPS via the induction of Th17 differentiation, and strategies that target these cytokines represent logical therapeutic approaches for IPS.
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