Critical link between TRAIL and CCL20 for the activation of TH2 cells and the expression of allergic airway disease

Markus Weckmann; Adam Collison; Jodie L. Simpson; Matthias V. Kopp; Peter A.B. Wark; Mark J. Smyth; Hideo Yagita; Klaus I. Matthaei; Nicole Hansbro; Bruce Whitehead; Peter G. Gibson; Paul S. Foster; Joerg Mattes

doi:10.1038/nm1660

Critical link between TRAIL and CCL20 for the activation of T_H2 cells and the expression of allergic airway disease

Markus Weckmann, Adam Collison, Jodie L. Simpson, Matthias V. Kopp, Peter A.B. Wark, Mark J. Smyth, Hideo Yagita, Klaus I. Matthaei, Nicole Hansbro, Bruce Whitehead, Peter G. Gibson, Paul S. Foster, Joerg Mattes^*

^*Corresponding author for this work

Clinic of Pediatric and Adolescent Medicine

94 Citations (Scopus)

Abstract

The role of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in immune responses mediated by T-helper 2 (T_H2) lymphocytes is unknown. Here we characterize the development of allergic airway disease in TRAIL-deficient (Tnfsf10^-/-) mice and in mice exposed to short interfering RNA targeting TRAIL. We show that TRAIL is abundantly expressed in the airway epithelium of allergic mice and that inhibition of signaling impairs production of the chemokine CCL20 and homing of myeloid dendritic cells and T cells expressing CCR6 and CD4 to the airways. Attenuated homing limits T _H2 cytokine release, inflammation, airway hyperreactivity and expression of the transcriptional activator STAT6. Activation of STAT6 by interleukin-13 restores airway hyperreactivity in Tnfsf10^-/- mice. Recombinant TRAIL induces pathognomic features of asthma and stimulates the production of CCL20 in primary human bronchial epithelium cells. TRAIL is also increased in sputum of asthmatics. The function of TRAIL in the airway epithelium identifies this molecule as a target for the treatment of asthma.

Original language	English
Journal	Nature Medicine
Volume	13
Issue number	11
Pages (from-to)	1308-1315
Number of pages	8
ISSN	1078-8956
DOIs	https://doi.org/10.1038/nm1660
Publication status	Published - 11.2007

Research Areas and Centers

Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/nm1660

Cite this

Weckmann, M., Collison, A., Simpson, J. L., Kopp, M. V., Wark, P. A. B., Smyth, M. J., Yagita, H., Matthaei, K. I., Hansbro, N., Whitehead, B., Gibson, P. G., Foster, P. S., & Mattes, J. (2007). Critical link between TRAIL and CCL20 for the activation of T_H2 cells and the expression of allergic airway disease. Nature Medicine, 13(11), 1308-1315. https://doi.org/10.1038/nm1660

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title = "Critical link between TRAIL and CCL20 for the activation of TH2 cells and the expression of allergic airway disease",

abstract = "The role of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in immune responses mediated by T-helper 2 (TH2) lymphocytes is unknown. Here we characterize the development of allergic airway disease in TRAIL-deficient (Tnfsf10-/-) mice and in mice exposed to short interfering RNA targeting TRAIL. We show that TRAIL is abundantly expressed in the airway epithelium of allergic mice and that inhibition of signaling impairs production of the chemokine CCL20 and homing of myeloid dendritic cells and T cells expressing CCR6 and CD4 to the airways. Attenuated homing limits T H2 cytokine release, inflammation, airway hyperreactivity and expression of the transcriptional activator STAT6. Activation of STAT6 by interleukin-13 restores airway hyperreactivity in Tnfsf10-/- mice. Recombinant TRAIL induces pathognomic features of asthma and stimulates the production of CCL20 in primary human bronchial epithelium cells. TRAIL is also increased in sputum of asthmatics. The function of TRAIL in the airway epithelium identifies this molecule as a target for the treatment of asthma.",

author = "Markus Weckmann and Adam Collison and Simpson, {Jodie L.} and Kopp, {Matthias V.} and Wark, {Peter A.B.} and Smyth, {Mark J.} and Hideo Yagita and Matthaei, {Klaus I.} and Nicole Hansbro and Bruce Whitehead and Gibson, {Peter G.} and Foster, {Paul S.} and Joerg Mattes",

note = "Funding Information: We thank H. Rosenberg and R. Kumar for comments on the manuscript; J. Peschon (AMGEN, USA) for Tnfsf10−/− mice; A.N. McKenzie (Cambridge, UK) for Il13−/− mice; and S. Driever, G. Korth, J.C. Simon and staff from the Animal Care Facility of the contributing institutes for technical assistance. This study was supported by the Landesstiftung Baden-Wuerttemberg, Forschungsprogramm {\textquoteleft}Allergologie{\textquoteright} (P-LS-AL/5 to J.M.), and in part by the Forschungskommission Universitaet Freiburg (J.M.), the Wissenschaftliche Gesellschaft Freiburg (J.M.), a National Health Medical Research Council (NH&MRC) Program Grant (J.M., K.I.M., P.S.F.), the Hunter Medical Research Institute (J.M., P.S.F.), a Jardine Lloyd Thompson Fellowship (J.M.) and an NH&MRC Program Grant and Research Fellowship (M.J.S.). Copyright: Copyright 2009 Elsevier B.V., All rights reserved.",

year = "2007",

month = nov,

doi = "10.1038/nm1660",

language = "English",

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pages = "1308--1315",

journal = "Nature Medicine",

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T1 - Critical link between TRAIL and CCL20 for the activation of TH2 cells and the expression of allergic airway disease

AU - Weckmann, Markus

AU - Collison, Adam

AU - Simpson, Jodie L.

AU - Kopp, Matthias V.

AU - Wark, Peter A.B.

AU - Smyth, Mark J.

AU - Yagita, Hideo

AU - Matthaei, Klaus I.

AU - Hansbro, Nicole

AU - Whitehead, Bruce

AU - Gibson, Peter G.

AU - Foster, Paul S.

AU - Mattes, Joerg

N1 - Funding Information: We thank H. Rosenberg and R. Kumar for comments on the manuscript; J. Peschon (AMGEN, USA) for Tnfsf10−/− mice; A.N. McKenzie (Cambridge, UK) for Il13−/− mice; and S. Driever, G. Korth, J.C. Simon and staff from the Animal Care Facility of the contributing institutes for technical assistance. This study was supported by the Landesstiftung Baden-Wuerttemberg, Forschungsprogramm ‘Allergologie’ (P-LS-AL/5 to J.M.), and in part by the Forschungskommission Universitaet Freiburg (J.M.), the Wissenschaftliche Gesellschaft Freiburg (J.M.), a National Health Medical Research Council (NH&MRC) Program Grant (J.M., K.I.M., P.S.F.), the Hunter Medical Research Institute (J.M., P.S.F.), a Jardine Lloyd Thompson Fellowship (J.M.) and an NH&MRC Program Grant and Research Fellowship (M.J.S.). Copyright: Copyright 2009 Elsevier B.V., All rights reserved.

PY - 2007/11

Y1 - 2007/11

N2 - The role of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in immune responses mediated by T-helper 2 (TH2) lymphocytes is unknown. Here we characterize the development of allergic airway disease in TRAIL-deficient (Tnfsf10-/-) mice and in mice exposed to short interfering RNA targeting TRAIL. We show that TRAIL is abundantly expressed in the airway epithelium of allergic mice and that inhibition of signaling impairs production of the chemokine CCL20 and homing of myeloid dendritic cells and T cells expressing CCR6 and CD4 to the airways. Attenuated homing limits T H2 cytokine release, inflammation, airway hyperreactivity and expression of the transcriptional activator STAT6. Activation of STAT6 by interleukin-13 restores airway hyperreactivity in Tnfsf10-/- mice. Recombinant TRAIL induces pathognomic features of asthma and stimulates the production of CCL20 in primary human bronchial epithelium cells. TRAIL is also increased in sputum of asthmatics. The function of TRAIL in the airway epithelium identifies this molecule as a target for the treatment of asthma.

AB - The role of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in immune responses mediated by T-helper 2 (TH2) lymphocytes is unknown. Here we characterize the development of allergic airway disease in TRAIL-deficient (Tnfsf10-/-) mice and in mice exposed to short interfering RNA targeting TRAIL. We show that TRAIL is abundantly expressed in the airway epithelium of allergic mice and that inhibition of signaling impairs production of the chemokine CCL20 and homing of myeloid dendritic cells and T cells expressing CCR6 and CD4 to the airways. Attenuated homing limits T H2 cytokine release, inflammation, airway hyperreactivity and expression of the transcriptional activator STAT6. Activation of STAT6 by interleukin-13 restores airway hyperreactivity in Tnfsf10-/- mice. Recombinant TRAIL induces pathognomic features of asthma and stimulates the production of CCL20 in primary human bronchial epithelium cells. TRAIL is also increased in sputum of asthmatics. The function of TRAIL in the airway epithelium identifies this molecule as a target for the treatment of asthma.

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