ICOS protects against mortality from acute lung injury through activation of IL-5 + ILC2s

C. L. Hrusch, S. T. Manns, D. Bryazka, J. Casaos, C. A. Bonham, M. R. Jaffery, K. M. Blaine, K. A.M. Mills, P. A. Verhoef, A. O. Adegunsoye, J. W. Williams, M. Y. Tjota, T. V. Moore, M. E. Strek, I. Noth, A. I. Sperling

Research output: Contribution to journalArticle

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Abstract

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 languageEnglish (US)
Pages (from-to)61-70
Number of pages10
JournalMucosal Immunology
Volume11
Issue number1
DOIs
StatePublished - Jan 1 2018
Externally publishedYes

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Acute Lung Injury
Interleukin-5
Idiopathic Pulmonary Fibrosis
Lung Injury
Lung
Mortality
Bleomycin
Survival
Acute Disease
Infection
Lung Diseases
Cicatrix
Blood Cells
Fibrosis
Therapeutics
Lymphocytes
T-Lymphocytes
Wounds and Injuries

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

Cite this

Hrusch, C. L., Manns, S. T., Bryazka, D., Casaos, J., Bonham, C. A., Jaffery, M. R., ... Sperling, A. I. (2018). ICOS protects against mortality from acute lung injury through activation of IL-5 + ILC2s. Mucosal Immunology, 11(1), 61-70. https://doi.org/10.1038/mi.2017.42

ICOS protects against mortality from acute lung injury through activation of IL-5 + ILC2s. / Hrusch, C. L.; Manns, S. T.; Bryazka, D.; Casaos, J.; Bonham, C. A.; Jaffery, M. R.; Blaine, K. M.; Mills, K. A.M.; Verhoef, P. A.; Adegunsoye, A. O.; Williams, J. W.; Tjota, M. Y.; Moore, T. V.; Strek, M. E.; Noth, I.; Sperling, A. I.

In: Mucosal Immunology, Vol. 11, No. 1, 01.01.2018, p. 61-70.

Research output: Contribution to journalArticle

Hrusch, CL, Manns, ST, Bryazka, D, Casaos, J, Bonham, CA, Jaffery, MR, Blaine, KM, Mills, KAM, Verhoef, PA, Adegunsoye, AO, Williams, JW, Tjota, MY, Moore, TV, Strek, ME, Noth, I & Sperling, AI 2018, 'ICOS protects against mortality from acute lung injury through activation of IL-5 + ILC2s', Mucosal Immunology, vol. 11, no. 1, pp. 61-70. https://doi.org/10.1038/mi.2017.42
Hrusch CL, Manns ST, Bryazka D, Casaos J, Bonham CA, Jaffery MR et al. ICOS protects against mortality from acute lung injury through activation of IL-5 + ILC2s. Mucosal Immunology. 2018 Jan 1;11(1):61-70. https://doi.org/10.1038/mi.2017.42
Hrusch, C. L. ; Manns, S. T. ; Bryazka, D. ; Casaos, J. ; Bonham, C. A. ; Jaffery, M. R. ; Blaine, K. M. ; Mills, K. A.M. ; Verhoef, P. A. ; Adegunsoye, A. O. ; Williams, J. W. ; Tjota, M. Y. ; Moore, T. V. ; Strek, M. E. ; Noth, I. ; Sperling, A. I. / ICOS protects against mortality from acute lung injury through activation of IL-5 + ILC2s. In: Mucosal Immunology. 2018 ; Vol. 11, No. 1. pp. 61-70.
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