Lung parenchyma-derived IL-6 promotes IL-17A-dependent acute lung injury after allogeneic stem cell transplantation

Varelias, Antiopi, Gartlan, Kate H., Kreijveld, Ellen, Olver, Stuart D., Lor, Mary, Kuns, Rachel D., Lineburg, Katie E., Teal, Bianca E., Raffelt, Neil C., Cheong, Melody, Alexander, Kylie A., Koyama, Motoko, Markey, Kate A., Sturgeon, Elise, Leach, Justine, Reddy, Pavan, Kennedy, Glen A., Yanik, Gregory A., Blazar, Bruce R., Tey, Siok-Keen, Clouston, Andrew D., MacDonald, Kelli P. A., Cooke, Kenneth R. and Hill, Geoffrey R. (2015) Lung parenchyma-derived IL-6 promotes IL-17A-dependent acute lung injury after allogeneic stem cell transplantation. Blood, 125 15: 2435-2444. doi:10.1182/blood-2014-07-590232

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Author Varelias, Antiopi
Gartlan, Kate H.
Kreijveld, Ellen
Olver, Stuart D.
Lor, Mary
Kuns, Rachel D.
Lineburg, Katie E.
Teal, Bianca E.
Raffelt, Neil C.
Cheong, Melody
Alexander, Kylie A.
Koyama, Motoko
Markey, Kate A.
Sturgeon, Elise
Leach, Justine
Reddy, Pavan
Kennedy, Glen A.
Yanik, Gregory A.
Blazar, Bruce R.
Tey, Siok-Keen
Clouston, Andrew D.
MacDonald, Kelli P. A.
Cooke, Kenneth R.
Hill, Geoffrey R.
Title Lung parenchyma-derived IL-6 promotes IL-17A-dependent acute lung injury after allogeneic stem cell transplantation
Journal name Blood   Check publisher's open access policy
ISSN 1528-0020
Publication date 2015-04-09
Year available 2015
Sub-type Article (original research)
DOI 10.1182/blood-2014-07-590232
Open Access Status Not Open Access
Volume 125
Issue 15
Start page 2435
End page 2444
Total pages 10
Place of publication Washington, DC United States
Publisher American Society of Hematology
Collection year 2016
Language eng
Formatted 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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Medicine Publications
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