IL-25 and type 2 innate lymphoid cells induce pulmonary fibrosis

Emily Hams; Michelle E. Armstrong; Jillian L. Barlow; Sean P. Saunders; Christian Schwartz; Gordon Cooke; Ruairi J. Fahy; Thomas B. Crotty; Nikhil Hirani; Robin J. Flynn; David Voehringer; Andrew N.J. McKenzie; Seamas C. Donnelly; Padraic G. Fallon

doi:10.1073/pnas.1315854111

IL-25 and type 2 innate lymphoid cells induce pulmonary fibrosis

Emily Hams, Michelle E. Armstrong, Jillian L. Barlow, Sean P. Saunders, Christian Schwartz, Gordon Cooke, Ruairi J. Fahy, Thomas B. Crotty, Nikhil Hirani, Robin J. Flynn, David Voehringer, Andrew N.J. McKenzie, Seamas C. Donnelly, Padraic G. Fallon

Research output: Contribution to journal › Article › peer-review

300 Citations (Scopus)

Abstract

Disease conditions associated with pulmonary fibrosis are progressive and have a poor long-term prognosis with irreversible changes in airway architecture leading to marked morbidity and mortalities. Using murine models we demonstrate a role for interleukin (IL)-25 in the generation of pulmonary fibrosis. Mechanistically, we identify IL-13 release from type 2 innate lymphoid cells (ILC2) as sufficient to drive collagen deposition in the lungs of challenged mice and suggest this as a potential mechanism through which IL-25 is acting. Additionally, we demonstrate that in human idiopathic pulmonary fibrosis there is increased pulmonary expression of IL-25 and also observe a population ILC2 in the lungs of idiopathic pulmonary fibrosis patients. Collectively, we present an innate mechanism for the generation of pulmonary fibrosis, via IL-25 and ILC2, that occurs independently of T-cell-mediated antigen-specific immune responses. These results suggest the potential of therapeutically targeting IL-25 and ILC2 for the treatment of human fibrotic diseases.

Original language	English
Pages (from-to)	367-372
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	111
Issue number	1
DOIs	https://doi.org/10.1073/pnas.1315854111
Publication status	Published - 2014
Externally published	Yes

Keywords

Cytokine
Inflammation
Innate response
Therapy

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10.1073/pnas.1315854111

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Hams, E., Armstrong, M. E., Barlow, J. L., Saunders, S. P., Schwartz, C., Cooke, G., Fahy, R. J., Crotty, T. B., Hirani, N., Flynn, R. J., Voehringer, D., McKenzie, A. N. J., Donnelly, S. C., & Fallon, P. G. (2014). IL-25 and type 2 innate lymphoid cells induce pulmonary fibrosis. Proceedings of the National Academy of Sciences of the United States of America, 111(1), 367-372. https://doi.org/10.1073/pnas.1315854111

@article{8fa85e1f9ca14fd3b85b319efac20f04,

title = "IL-25 and type 2 innate lymphoid cells induce pulmonary fibrosis",

abstract = "Disease conditions associated with pulmonary fibrosis are progressive and have a poor long-term prognosis with irreversible changes in airway architecture leading to marked morbidity and mortalities. Using murine models we demonstrate a role for interleukin (IL)-25 in the generation of pulmonary fibrosis. Mechanistically, we identify IL-13 release from type 2 innate lymphoid cells (ILC2) as sufficient to drive collagen deposition in the lungs of challenged mice and suggest this as a potential mechanism through which IL-25 is acting. Additionally, we demonstrate that in human idiopathic pulmonary fibrosis there is increased pulmonary expression of IL-25 and also observe a population ILC2 in the lungs of idiopathic pulmonary fibrosis patients. Collectively, we present an innate mechanism for the generation of pulmonary fibrosis, via IL-25 and ILC2, that occurs independently of T-cell-mediated antigen-specific immune responses. These results suggest the potential of therapeutically targeting IL-25 and ILC2 for the treatment of human fibrotic diseases.",

keywords = "Cytokine, Inflammation, Innate response, Therapy",

author = "Emily Hams and Armstrong, {Michelle E.} and Barlow, {Jillian L.} and Saunders, {Sean P.} and Christian Schwartz and Gordon Cooke and Fahy, {Ruairi J.} and Crotty, {Thomas B.} and Nikhil Hirani and Flynn, {Robin J.} and David Voehringer and McKenzie, {Andrew N.J.} and Donnelly, {Seamas C.} and Fallon, {Padraic G.}",

year = "2014",

doi = "10.1073/pnas.1315854111",

language = "English",

volume = "111",

pages = "367--372",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

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Hams, E, Armstrong, ME, Barlow, JL, Saunders, SP, Schwartz, C, Cooke, G, Fahy, RJ, Crotty, TB, Hirani, N, Flynn, RJ, Voehringer, D, McKenzie, ANJ, Donnelly, SC & Fallon, PG 2014, 'IL-25 and type 2 innate lymphoid cells induce pulmonary fibrosis', Proceedings of the National Academy of Sciences of the United States of America, vol. 111, no. 1, pp. 367-372. https://doi.org/10.1073/pnas.1315854111

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T1 - IL-25 and type 2 innate lymphoid cells induce pulmonary fibrosis

AU - Hams, Emily

AU - Armstrong, Michelle E.

AU - Barlow, Jillian L.

AU - Saunders, Sean P.

AU - Schwartz, Christian

AU - Cooke, Gordon

AU - Fahy, Ruairi J.

AU - Crotty, Thomas B.

AU - Hirani, Nikhil

AU - Flynn, Robin J.

AU - Voehringer, David

AU - McKenzie, Andrew N.J.

AU - Donnelly, Seamas C.

AU - Fallon, Padraic G.

PY - 2014

Y1 - 2014

N2 - Disease conditions associated with pulmonary fibrosis are progressive and have a poor long-term prognosis with irreversible changes in airway architecture leading to marked morbidity and mortalities. Using murine models we demonstrate a role for interleukin (IL)-25 in the generation of pulmonary fibrosis. Mechanistically, we identify IL-13 release from type 2 innate lymphoid cells (ILC2) as sufficient to drive collagen deposition in the lungs of challenged mice and suggest this as a potential mechanism through which IL-25 is acting. Additionally, we demonstrate that in human idiopathic pulmonary fibrosis there is increased pulmonary expression of IL-25 and also observe a population ILC2 in the lungs of idiopathic pulmonary fibrosis patients. Collectively, we present an innate mechanism for the generation of pulmonary fibrosis, via IL-25 and ILC2, that occurs independently of T-cell-mediated antigen-specific immune responses. These results suggest the potential of therapeutically targeting IL-25 and ILC2 for the treatment of human fibrotic diseases.

AB - Disease conditions associated with pulmonary fibrosis are progressive and have a poor long-term prognosis with irreversible changes in airway architecture leading to marked morbidity and mortalities. Using murine models we demonstrate a role for interleukin (IL)-25 in the generation of pulmonary fibrosis. Mechanistically, we identify IL-13 release from type 2 innate lymphoid cells (ILC2) as sufficient to drive collagen deposition in the lungs of challenged mice and suggest this as a potential mechanism through which IL-25 is acting. Additionally, we demonstrate that in human idiopathic pulmonary fibrosis there is increased pulmonary expression of IL-25 and also observe a population ILC2 in the lungs of idiopathic pulmonary fibrosis patients. Collectively, we present an innate mechanism for the generation of pulmonary fibrosis, via IL-25 and ILC2, that occurs independently of T-cell-mediated antigen-specific immune responses. These results suggest the potential of therapeutically targeting IL-25 and ILC2 for the treatment of human fibrotic diseases.

KW - Cytokine

KW - Inflammation

KW - Innate response

KW - Therapy

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JF - Proceedings of the National Academy of Sciences of the United States of America

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ER -

IL-25 and type 2 innate lymphoid cells induce pulmonary fibrosis

Abstract

Keywords

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