Deletion of mtorc1 activity in CD4+ T cells is associated with lung fibrosis and increased γδ T cells
Public Deposited- Creator
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Vigeland, C.L.
- Affiliation: School of Medicine, Department of Medicine
- Other Affiliation: Johns Hopkins University School of Medicine
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Collins, S.L.
- Other Affiliation: Johns Hopkins University School of Medicine
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Chan-Li, Y.
- Other Affiliation: Johns Hopkins University School of Medicine
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Hughes, A.H.
- Other Affiliation: Johns Hopkins University School of Medicine
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Oh, M.-H.
- Other Affiliation: Johns Hopkins University School of Medicine
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Powell, J.D.
- Other Affiliation: Johns Hopkins University School of Medicine
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Horton, M.R.
- Other Affiliation: Johns Hopkins University School of Medicine
- Abstract
- Pulmonary fibrosis is a devastating, incurable disease in which chronic inflammation and dysregulated, excessive wound healing lead to progressive fibrosis, lung dysfunction, and ultimately death. Prior studies have implicated the cytokine IL-17A and Th17 cells in promoting the development of fibrosis. We hypothesized that loss of Th17 cells via CD4-specific deletion of mTORC1 activity would abrogate the development of bleomycin-induced pulmonary fibrosis. However, in actuality loss of Th17 cells led to increased mortality and fibrosis in response to bleomycin. We found that in the absence of Th17 cells, there was continued production of IL-17A by γδT cells. These IL-17A+γδT cells were associated with increased lung neutrophils and M2 macrophages, accelerated development of fibrosis, and increased mortality. These data elucidate the critical role of IL-17A+ γδT cells in promoting chronic inflammation and fibrosis, and reveal a novel therapeutic target for treatment of pulmonary fibrosis.
- Date of publication
- 2016
- Keyword
- DOI
- Identifier
- PMID 27649073
- https://dx.doi.org/10.1371/journal.pone.0163288
- Resource type
- Article
- Rights statement
- In Copyright
- License
- Attribution 3.0 United States
- Journal title
- PLoS ONE
- Journal volume
- 11
- Journal issue
- 9
- Language
- English
- ISSN
- 1932-6203
- Publisher
- Public Library of Science
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