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Regulated on Activation, Normal T Cell Expressed and Secreted Drives the Resolution of Allergic Asthma

42 Pages Posted: 30 Dec 2020 Publication Status: Published

See all articles by Nina Li

Nina Li

University of Erlangen-Nuremberg-Friedrich Alexander Universität Erlangen Nürnberg - Department of Molecular Pneumology

Hoomann Mirzakhani

Harvard Medical School - Channing Division of Network Medicine

Alexander Kiefer

Friedrich-Alexander-Universität Erlangen-Nürnberg - Department of Allergy and Pneumology

Julia Koelle

University of Erlangen-Nuremberg-Friedrich Alexander Universität Erlangen Nürnberg - Department of Molecular Pneumology

Tytti Vuorinen

Turku University Hospital - Department of Clinical Microbiology

Manfred Rauh

Friedrich-Alexander-Universität Erlangen-Nürnberg - Department of Allergy and Pneumology

Paraskevi Xepapadaki

National Kapodistrian University of Athens - Department of Allergy

Anna Lewandowska-Polak

Medical University of Lodz - Department of Rheumatology and Allergy

Heikki Lukkarinen

University of Turku - Department of Pediatrics

Nan Zhang

University of Gent - Upper Airways Research Laboratory

Barbara Stanic

University of Zurich - Swiss Institute of Allergy and Asthma Research (SIAF)

Theodor Zimmermann

Friedrich-Alexander-Universität Erlangen-Nürnberg - Department of Allergy and Pneumology

Marek L. Kowalski

Medical University of Lodz - Department of Rheumatology and Allergy

Tuomas Jiartti

University of Turku - Department of Pediatrics

Claus Bachert

University of Gent - Upper Airways Research Laboratory

Mubeccel Akdis

University of Zurich - Swiss Institute of Allergy and Asthma Research (SIAF)

Nikolaos G. Papadopoulos

National Kapodistrian University of Athens - Department of Allergy

Benjamin A. Raby

Harvard Medical School - Channing Division of Network Medicine

Scott T. Weiss

Harvard Medical School - Channing Division of Network Medicine

Susetta Finotto

University of Erlangen-Nuremberg-Friedrich Alexander Universität Erlangen Nürnberg - Department of Molecular Pneumology

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Abstract

RANTES has been implicated in allergic asthma as well as in T cell-dependent clearance of infection. RANTES receptor is a G-protein coupled, seven-transmembrane receptor which comprises CCR1, CCR3 and CCR5. Infections with respiratory viruses cause induction of RANTES by epithelial cells. Here, we studied the role of RANTES in PBMC from several cohorts of children with and without asthma recruited within the European study Predicta and extended this study to the airways of adults with and without asthma recruited in the Asthma BRIDGE study in the USA. We further translated these studies to murine models of asthma induced by house dust mite (HDM) in wild type RANTES and CCR5 deficient mice. Here we show an unpredicted therapeutic role of RANTES in the resolution of allergen induced asthma by orchestrating the transition from effector GATA-3+ CD4+ T cells and inflammatory eosinophils into immunoregulatory type T cells and resident eosinophils.

Keywords: RANTES, CCR5, allergic asthma, rhinovirus, Th2 cells, resident eosinophils, inflammatory eosinophils,GATA3, Interferon, TLR7/8 agonists

Suggested Citation

Li, Nina and Mirzakhani, Hoomann and Kiefer, Alexander and Koelle, Julia and Vuorinen, Tytti and Rauh, Manfred and Xepapadaki, Paraskevi and Lewandowska-Polak, Anna and Lukkarinen, Heikki and Zhang, Nan and Stanic, Barbara and Zimmermann, Theodor and Kowalski, Marek L. and Jiartti, Tuomas and Bachert, Claus and Akdis, Mubeccel and Papadopoulos, Nikolaos G. and Raby, Benjamin A. and Weiss, Scott T. and Finotto, Susetta, Regulated on Activation, Normal T Cell Expressed and Secreted Drives the Resolution of Allergic Asthma. Available at SSRN: https://ssrn.com/abstract=3757688 or http://dx.doi.org/10.2139/ssrn.3757688
This version of the paper has not been formally peer reviewed.

Nina Li

University of Erlangen-Nuremberg-Friedrich Alexander Universität Erlangen Nürnberg - Department of Molecular Pneumology

Germany

Hoomann Mirzakhani

Harvard Medical School - Channing Division of Network Medicine ( email )

75 Francis St.
Boston, MA 02115
United States

Alexander Kiefer

Friedrich-Alexander-Universität Erlangen-Nürnberg - Department of Allergy and Pneumology

Lange Gasse 20
Lange Gasse 20,
Nürnberg, 90403
Germany

Julia Koelle

University of Erlangen-Nuremberg-Friedrich Alexander Universität Erlangen Nürnberg - Department of Molecular Pneumology

Germany

Tytti Vuorinen

Turku University Hospital - Department of Clinical Microbiology ( email )

Turku, 20014
Finland

Manfred Rauh

Friedrich-Alexander-Universität Erlangen-Nürnberg - Department of Allergy and Pneumology

Lange Gasse 20
Lange Gasse 20,
Nürnberg, 90403
Germany

Paraskevi Xepapadaki

National Kapodistrian University of Athens - Department of Allergy ( email )

5 Stadiou Strt
Athens, 12131
Greece

Anna Lewandowska-Polak

Medical University of Lodz - Department of Rheumatology and Allergy ( email )

Lodz
Poland

Heikki Lukkarinen

University of Turku - Department of Pediatrics ( email )

Turku, 20014
Finland

Nan Zhang

University of Gent - Upper Airways Research Laboratory

Coupure Links 653
Gent, 9000
Belgium

Barbara Stanic

University of Zurich - Swiss Institute of Allergy and Asthma Research (SIAF) ( email )

Rämistrasse 71
Zürich, CH-8006
Switzerland

Theodor Zimmermann

Friedrich-Alexander-Universität Erlangen-Nürnberg - Department of Allergy and Pneumology ( email )

Lange Gasse 20
Lange Gasse 20,
Nürnberg, 90403
Germany

Marek L. Kowalski

Medical University of Lodz - Department of Rheumatology and Allergy ( email )

Lodz
Poland

Tuomas Jiartti

University of Turku - Department of Pediatrics ( email )

Turku, 20014
Finland

Claus Bachert

University of Gent - Upper Airways Research Laboratory ( email )

Coupure Links 653
Gent, 9000
Belgium

Mubeccel Akdis

University of Zurich - Swiss Institute of Allergy and Asthma Research (SIAF) ( email )

Rämistrasse 71
Zürich, CH-8006
Switzerland

Nikolaos G. Papadopoulos

National Kapodistrian University of Athens - Department of Allergy

5 Stadiou Strt
Athens, 12131
Greece

Benjamin A. Raby

Harvard Medical School - Channing Division of Network Medicine ( email )

75 Francis St.
Boston, MA 02115
United States

Scott T. Weiss

Harvard Medical School - Channing Division of Network Medicine ( email )

75 Francis St.
Boston, MA 02115
United States

Susetta Finotto (Contact Author)

University of Erlangen-Nuremberg-Friedrich Alexander Universität Erlangen Nürnberg - Department of Molecular Pneumology ( email )

Germany

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