Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus

Laurel A. Monticelli; Gregory F. Sonnenberg; Michael C. Abt; Theresa Alenghat; Carly G.K. Ziegler; Travis A. Doering; Jill M. Angelosanto; Brian J. Laidlaw; Cliff Y. Yang; Taheri Sathaliyawala; Masaru Kubota; Damian Turner; Joshua M. Diamond; Ananda W. Goldrath; Donna L. Farber; Ronald G. Collman; E. John Wherry; David Artis

doi:10.1038/ni.2131

Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus

Laurel A. Monticelli, Gregory F. Sonnenberg, Michael C. Abt, Theresa Alenghat, Carly G.K. Ziegler, Travis A. Doering, Jill M. Angelosanto, Brian J. Laidlaw, Cliff Y. Yang, Taheri Sathaliyawala, Masaru Kubota, Damian Turner, Joshua M. Diamond, Ananda W. Goldrath, Donna L. Farber, Ronald G. Collman, E. John Wherry, David Artis

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1260 Scopus citations

Abstract

Innate lymphoid cells (ILCs), a heterogeneous cell population, are critical in orchestrating immunity and inflammation in the intestine, but whether ILCs influence immune responses or tissue homeostasis at other mucosal sites remains poorly characterized. Here we identify a population of lung-resident ILCs in mice and humans that expressed the alloantigen Thy-1 (CD90), interleukin 2 (IL-2) receptor α-chain (CD25), IL-7 receptor α-chain (CD127) and the IL-33 receptor subunit T1-ST2. Notably, mouse ILCs accumulated in the lung after infection with influenza virus, and depletion of ILCs resulted in loss of airway epithelial integrity, diminished lung function and impaired airway remodeling. These defects were restored by administration of the lung ILC product amphiregulin. Collectively, our results demonstrate a critical role for lung ILCs in restoring airway epithelial integrity and tissue homeostasis after infection with influenza virus.

Original language	English
Pages (from-to)	1045-1054
Number of pages	10
Journal	Nature immunology
Volume	12
Issue number	11
DOIs	https://doi.org/10.1038/ni.2131
State	Published - Nov 2011

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Monticelli, L. A., Sonnenberg, G. F., Abt, M. C., Alenghat, T., Ziegler, C. G. K., Doering, T. A., Angelosanto, J. M., Laidlaw, B. J., Yang, C. Y., Sathaliyawala, T., Kubota, M., Turner, D., Diamond, J. M., Goldrath, A. W., Farber, D. L., Collman, R. G., Wherry, E. J., & Artis, D. (2011). Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus. Nature immunology, 12(11), 1045-1054. https://doi.org/10.1038/ni.2131

@article{fdb7ac56ee5f44ce911ff8f0f2bf8cc3,

title = "Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus",

abstract = "Innate lymphoid cells (ILCs), a heterogeneous cell population, are critical in orchestrating immunity and inflammation in the intestine, but whether ILCs influence immune responses or tissue homeostasis at other mucosal sites remains poorly characterized. Here we identify a population of lung-resident ILCs in mice and humans that expressed the alloantigen Thy-1 (CD90), interleukin 2 (IL-2) receptor α-chain (CD25), IL-7 receptor α-chain (CD127) and the IL-33 receptor subunit T1-ST2. Notably, mouse ILCs accumulated in the lung after infection with influenza virus, and depletion of ILCs resulted in loss of airway epithelial integrity, diminished lung function and impaired airway remodeling. These defects were restored by administration of the lung ILC product amphiregulin. Collectively, our results demonstrate a critical role for lung ILCs in restoring airway epithelial integrity and tissue homeostasis after infection with influenza virus.",

author = "Monticelli, {Laurel A.} and Sonnenberg, {Gregory F.} and Abt, {Michael C.} and Theresa Alenghat and Ziegler, {Carly G.K.} and Doering, {Travis A.} and Angelosanto, {Jill M.} and Laidlaw, {Brian J.} and Yang, {Cliff Y.} and Taheri Sathaliyawala and Masaru Kubota and Damian Turner and Diamond, {Joshua M.} and Goldrath, {Ananda W.} and Farber, {Donna L.} and Collman, {Ronald G.} and Wherry, {E. John} and David Artis",

note = "Funding Information: We thank all members of the Artis and Wherry laboratories; M. Siracusa, S. Saenz, L. Osborne, E. Tait Wojno, M. Noti, M. Nair and A. Crawford for discussions and critical reading of the manuscript; D. Kobuley and D. Hill for care of the germ-free mouse facility; Yadav and A. Fitzgerald for assistance with the human BAL samples; and L. Fouser, S. Olland, R. Zollner, K. Lam and A. Root (Pfizer) for the preparation of anti-IL-22. Supported by US National Institutes of Health (U19AI083022, AI071309 and HHSN266200500030C to E.J.W.; HL098957 to R.G.C. for human pulmonary BAL studies; AI061570, AI074878, AI087990, AI095608, AI091759, AI095466 and U01AI095608 to D.A.; T32AI007532 to L.A.M. and G.F.S.; and T32AI05528 to M.C.A.), the Burroughs Wellcome Fund (D.A.), the National Institute of Diabetes and Digestive and Kidney Diseases Center for the Molecular Studies in Digestive and Liver Diseases Molecular Pathology and Imaging Core (DK50306) and the University of Pennsylvania (D.A.).",

year = "2011",

month = nov,

doi = "10.1038/ni.2131",

language = "English",

volume = "12",

pages = "1045--1054",

journal = "Nature immunology",

issn = "1529-2908",

number = "11",

}

Monticelli, LA, Sonnenberg, GF, Abt, MC, Alenghat, T, Ziegler, CGK, Doering, TA, Angelosanto, JM, Laidlaw, BJ, Yang, CY, Sathaliyawala, T, Kubota, M, Turner, D, Diamond, JM, Goldrath, AW, Farber, DL, Collman, RG, Wherry, EJ & Artis, D 2011, 'Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus', Nature immunology, vol. 12, no. 11, pp. 1045-1054. https://doi.org/10.1038/ni.2131

TY - JOUR

T1 - Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus

AU - Monticelli, Laurel A.

AU - Sonnenberg, Gregory F.

AU - Abt, Michael C.

AU - Alenghat, Theresa

AU - Ziegler, Carly G.K.

AU - Doering, Travis A.

AU - Angelosanto, Jill M.

AU - Laidlaw, Brian J.

AU - Yang, Cliff Y.

AU - Sathaliyawala, Taheri

AU - Kubota, Masaru

AU - Turner, Damian

AU - Diamond, Joshua M.

AU - Goldrath, Ananda W.

AU - Farber, Donna L.

AU - Collman, Ronald G.

AU - Wherry, E. John

AU - Artis, David

N1 - Funding Information: We thank all members of the Artis and Wherry laboratories; M. Siracusa, S. Saenz, L. Osborne, E. Tait Wojno, M. Noti, M. Nair and A. Crawford for discussions and critical reading of the manuscript; D. Kobuley and D. Hill for care of the germ-free mouse facility; Yadav and A. Fitzgerald for assistance with the human BAL samples; and L. Fouser, S. Olland, R. Zollner, K. Lam and A. Root (Pfizer) for the preparation of anti-IL-22. Supported by US National Institutes of Health (U19AI083022, AI071309 and HHSN266200500030C to E.J.W.; HL098957 to R.G.C. for human pulmonary BAL studies; AI061570, AI074878, AI087990, AI095608, AI091759, AI095466 and U01AI095608 to D.A.; T32AI007532 to L.A.M. and G.F.S.; and T32AI05528 to M.C.A.), the Burroughs Wellcome Fund (D.A.), the National Institute of Diabetes and Digestive and Kidney Diseases Center for the Molecular Studies in Digestive and Liver Diseases Molecular Pathology and Imaging Core (DK50306) and the University of Pennsylvania (D.A.).

PY - 2011/11

Y1 - 2011/11

N2 - Innate lymphoid cells (ILCs), a heterogeneous cell population, are critical in orchestrating immunity and inflammation in the intestine, but whether ILCs influence immune responses or tissue homeostasis at other mucosal sites remains poorly characterized. Here we identify a population of lung-resident ILCs in mice and humans that expressed the alloantigen Thy-1 (CD90), interleukin 2 (IL-2) receptor α-chain (CD25), IL-7 receptor α-chain (CD127) and the IL-33 receptor subunit T1-ST2. Notably, mouse ILCs accumulated in the lung after infection with influenza virus, and depletion of ILCs resulted in loss of airway epithelial integrity, diminished lung function and impaired airway remodeling. These defects were restored by administration of the lung ILC product amphiregulin. Collectively, our results demonstrate a critical role for lung ILCs in restoring airway epithelial integrity and tissue homeostasis after infection with influenza virus.

AB - Innate lymphoid cells (ILCs), a heterogeneous cell population, are critical in orchestrating immunity and inflammation in the intestine, but whether ILCs influence immune responses or tissue homeostasis at other mucosal sites remains poorly characterized. Here we identify a population of lung-resident ILCs in mice and humans that expressed the alloantigen Thy-1 (CD90), interleukin 2 (IL-2) receptor α-chain (CD25), IL-7 receptor α-chain (CD127) and the IL-33 receptor subunit T1-ST2. Notably, mouse ILCs accumulated in the lung after infection with influenza virus, and depletion of ILCs resulted in loss of airway epithelial integrity, diminished lung function and impaired airway remodeling. These defects were restored by administration of the lung ILC product amphiregulin. Collectively, our results demonstrate a critical role for lung ILCs in restoring airway epithelial integrity and tissue homeostasis after infection with influenza virus.

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U2 - 10.1038/ni.2131

DO - 10.1038/ni.2131

M3 - Article

AN - SCOPUS:85027948313

SN - 1529-2908

VL - 12

SP - 1045

EP - 1054

JO - Nature immunology

JF - Nature immunology

IS - 11

ER -

Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus

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