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; Seamus 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, Seamus C Donnelly, Padraic G Fallon

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

Abstract / Description of output

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)	362-72
Journal	Proceedings of the National Academy of Sciences (PNAS)
Volume	111
Issue number	1
Early online date	16 Dec 2013
DOIs	https://doi.org/10.1073/pnas.1315854111
Publication status	Published - 7 Jan 2014

Keywords / Materials (for Non-textual outputs)

Aged
Animals
Cell Adhesion Molecules
Collagen
Female
Gene Expression Regulation
Humans
Idiopathic Pulmonary Fibrosis
Immunity, Innate
Inflammation
Interleukin-13
Interleukin-17
Liver
Lung
Lymphocytes
MALE
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Middle Aged
Pulmonary Fibrosis
Schistosoma mansoni

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10.1073/pnas.1315854111

http://www.pnas.org/content/111/1/367.long

Nikhil Hirani
- n.hiranied.acuk
Person: Academic: Research Active

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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 (PNAS), 111(1), 362-72. https://doi.org/10.1073/pnas.1315854111

@article{03486aaa088442c29862e0de2bb33f57,

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 = "Aged, Animals, Cell Adhesion Molecules, Collagen, Female, Gene Expression Regulation, Humans, Idiopathic Pulmonary Fibrosis, Immunity, Innate, Inflammation, Interleukin-13, Interleukin-17, Liver, Lung, Lymphocytes, MALE , Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Middle Aged, Pulmonary Fibrosis, Schistosoma mansoni",

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, {Seamus C} and Fallon, {Padraic G}",

year = "2014",

month = jan,

day = "7",

doi = "10.1073/pnas.1315854111",

language = "English",

volume = "111",

pages = "362--72",

journal = "Proceedings of the National Academy of Sciences (PNAS)",

issn = "0027-8424",

publisher = "National Academy of Sciences",

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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 (PNAS), vol. 111, no. 1, pp. 362-72. https://doi.org/10.1073/pnas.1315854111

TY - JOUR

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, Seamus C

AU - Fallon, Padraic G

PY - 2014/1/7

Y1 - 2014/1/7

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 - Aged

KW - Animals

KW - Cell Adhesion Molecules

KW - Collagen

KW - Female

KW - Gene Expression Regulation

KW - Humans

KW - Idiopathic Pulmonary Fibrosis

KW - Immunity, Innate

KW - Inflammation

KW - Interleukin-13

KW - Interleukin-17

KW - Liver

KW - Lung

KW - Lymphocytes

KW - MALE

KW - Mice

KW - Mice, Inbred BALB C

KW - Mice, Inbred C57BL

KW - Middle Aged

KW - Pulmonary Fibrosis

KW - Schistosoma mansoni

U2 - 10.1073/pnas.1315854111

DO - 10.1073/pnas.1315854111

M3 - Article

SN - 0027-8424

VL - 111

SP - 362

EP - 372

JO - Proceedings of the National Academy of Sciences (PNAS)

JF - Proceedings of the National Academy of Sciences (PNAS)

IS - 1

ER -

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

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Keywords / Materials (for Non-textual outputs)

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Nikhil Hirani

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