Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease causing irreversible lung scarring and loss of pulmonary function. IPF Patients suffer from a high rate of pulmonary infections and acute exacerbations of disease that further contribute to pulmonary decline. Low expression of the inducible T-cell costimulatory molecule (ICOS) in peripheral blood mononuclear cells predicts decreased survival of IPF patients, but the mechanisms by which ICOS protects are unclear. Using a model of bleomycin-induced lung injury and fibrosis, we now demonstrate that ICOS expression enhances survival from lung injury rather than regulating fibrogenesis. Of ICOS-expressing cells, type 2 innate lymphocytes (ILC2s) are the first to respond to bleomycin-induced injury, and this expansion is ICOS dependent. Interestingly, a similar decrease in ICOS + ILCs was found in lung tissue from IPF patients. Interleukin (IL)-5, produced primarily by ILC2s, was significantly reduced after lung injury in ICOS mice, and strikingly, treatment with IL-5 protected both ICOS and wild-type mice from mortality. These results imply that low ICOS expression and decreased lung ILC2s in IPF patients may contribute to poor recovery from infections and acute exacerbation and that IL-5 treatment may be a novel therapeutic strategy to overcome these defects and protect against lung injury.
|Original language||English (US)|
|Number of pages||10|
|State||Published - Jan 1 2018|
Bibliographical noteFunding Information:
We thank the IPF patients and families who generously agreed to participate in this study, the University of Chicago IPF transplant team and surgeons, especially Dr Edward Garrity, Dr Chris Wigfield, Dr Wickii Vigneswaran, and Dr Takeyoshi Ota. For facilitating the Gift of Hope control lung donations, we thank the Lung Biospeciman Core, especially Dr Julian Solway and Dr Steve White. We also thank Dr Amanda Marzo for her assistance with the murine influenza model. This work was supported by R21 AI126031; the University of Chicago Institute for Translational Medicine (ITM) Clinical and Translational Science Award UL1 RR024999; the IPFnet Cowlin Fellowship Award to S.T.M.; T32 HL007605 to C.L.H., S.T.M., C.A.B. and A.O.A.; 1R25 HL096383; and a supplement to U19 AI095230 to J.C. The University of Chicago Flow Cytometry Core is supported by P30 CA014599.
PubMed: MeSH publication types
- Journal Article
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't