Title |
Lung parenchyma-derived IL-6 promotes IL-17A–dependent acute lung injury after allogeneic stem cell transplantation
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Published in |
Blood, February 2015
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DOI | 10.1182/blood-2014-07-590232 |
Pubmed ID | |
Authors |
Antiopi Varelias, Kate H Gartlan, Ellen Kreijveld, Stuart D Olver, Mary Lor, Rachel D Kuns, Katie E Lineburg, Bianca E Teal, Neil C Raffelt, Melody Cheong, Kylie A Alexander, Motoko Koyama, Kate A Markey, Elise Sturgeon, Justine Leach, Pavan Reddy, Glen A Kennedy, Gregory A Yanik, Bruce R Blazar, Siok-Keen Tey, Andrew D Clouston, Kelli P A MacDonald, Kenneth R Cooke, Geoffrey R Hill |
Abstract |
Idiopathic Pneumonia Syndrome (IPS) is a relatively common, frequently fatal clinical entity characterized by non-infectious acute lung inflammation following allogeneic stem cell transplantation (SCT), the mechanisms of which are unclear. Here we demonstrate that immune suppression with cyclosporin after SCT limits Th1 differentiation and IFNγ secretion by donor T cells which is critical for inhibiting 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 was present at very high levels in the plasma of patients with IPS compared to SCT recipients without complications. Furthermore, at the time of diagnosis, plasma IL-6 levels were higher in a subset of IPS patients who were non-responsive to steroids and anti-TNF 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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Unknown | 1 | 100% |
Demographic breakdown
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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United States | 1 | 2% |
Unknown | 50 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 10 | 20% |
Student > Ph. D. Student | 6 | 12% |
Student > Master | 6 | 12% |
Student > Bachelor | 4 | 8% |
Professor > Associate Professor | 4 | 8% |
Other | 12 | 24% |
Unknown | 9 | 18% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 21 | 41% |
Biochemistry, Genetics and Molecular Biology | 6 | 12% |
Immunology and Microbiology | 5 | 10% |
Engineering | 2 | 4% |
Agricultural and Biological Sciences | 1 | 2% |
Other | 5 | 10% |
Unknown | 11 | 22% |