Deletion of mtorc1 activity in CD4+ T cells is associated with lung fibrosis and increased γδ T cells

Christine L. Vigeland, Samuel Lester Collins, Yee Chan-Li, Andrew Hughes, Min Hee Oh, Jonathan Powell, Maureen Horton

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere0163288
JournalPLoS One
Volume11
Issue number9
DOIs
StatePublished - Sep 1 2016

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T-cells
Interleukin-17
Th17 Cells
fibrosis
Fibrosis
T-lymphocytes
lungs
Pulmonary Fibrosis
T-Lymphocytes
Lung
Bleomycin
Macrophages
Inflammation
Mortality
inflammation
Wound Healing
cells
Cytokines
Neutrophils
tissue repair

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Deletion of mtorc1 activity in CD4+ T cells is associated with lung fibrosis and increased γδ T cells. / Vigeland, Christine L.; Collins, Samuel Lester; Chan-Li, Yee; Hughes, Andrew; Oh, Min Hee; Powell, Jonathan; Horton, Maureen.

In: PLoS One, Vol. 11, No. 9, e0163288, 01.09.2016.

Research output: Contribution to journalArticle

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AU - Oh, Min Hee

AU - Powell, Jonathan

AU - Horton, Maureen

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