iScience (Oct 2021)
Regulated on Activation, Normal T cell Expressed and Secreted (RANTES) drives the resolution of allergic asthma
- Nina Li,
- Hoomann Mirzakhani,
- Alexander Kiefer,
- Julia Koelle,
- Tytti Vuorinen,
- Manfred Rauh,
- Zuqin Yang,
- Susanne Krammer,
- Paraskevi Xepapadaki,
- Anna Lewandowska-Polak,
- Heikki Lukkarinen,
- Nan Zhang,
- Barbara Stanic,
- Theodor Zimmermann,
- Marek L. Kowalski,
- Tuomas Jartti,
- Claus Bachert,
- Mübeccel Akdis,
- Nikolaos G. Papadopoulos,
- Benjamin A. Raby,
- Scott T. Weiss,
- Susetta Finotto
Affiliations
- Nina Li
- Department of Molecular Pneumology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany
- Hoomann Mirzakhani
- Channing Division of Network Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
- Alexander Kiefer
- Department of Allergy and Pneumology, Children’s Hospital, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany
- Julia Koelle
- Department of Molecular Pneumology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany
- Tytti Vuorinen
- Medical Microbiology, Turku University Hospital, Institut of Biomedicine, University of Turku, Turku, Finland
- Manfred Rauh
- Department of Allergy and Pneumology, Children’s Hospital, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany
- Zuqin Yang
- Department of Molecular Pneumology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany
- Susanne Krammer
- Department of Molecular Pneumology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany
- Paraskevi Xepapadaki
- Department of Allergy, 2nd Pediatric Clinic, National and Kapodistrian University of Athens, Athens, Greece
- Anna Lewandowska-Polak
- Department of Rheumatology, Medical University of Lodz, Lodz, Poland
- Heikki Lukkarinen
- Department of Pediatrics and Adolescent Medicine, Turku University Hospital and University of Turku, Turku, Finland
- Nan Zhang
- Upper Airways Research Laboratory, Otorhinolaryngology, University of Gent, Gent, Belgium
- Barbara Stanic
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Herman-Burchard-Strasse 9, Davos, Switzerland
- Theodor Zimmermann
- Department of Allergy and Pneumology, Children’s Hospital, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany
- Marek L. Kowalski
- Department of Immunology and Allergy, Medical University of Lodz, Poland
- Tuomas Jartti
- Department of Pediatrics and Adolescent Medicine, Turku University Hospital and University of Turku, Turku, Finland; PEDEGO Research Unit, Medical Research Center, University of Oulu, Oulu, Finland; Department of Pediatrics and Adolescent Medicine, Oulu University Hospital, Oulu, Finland
- Claus Bachert
- Upper Airways Research Laboratory, Otorhinolaryngology, University of Gent, Gent, Belgium
- Mübeccel Akdis
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Herman-Burchard-Strasse 9, Davos, Switzerland
- Nikolaos G. Papadopoulos
- Department of Allergy, 2nd Pediatric Clinic, National and Kapodistrian University of Athens, Athens, Greece; Centre for Respiratory Medicine & Allergy, University of Manchester, Manchester, UK
- Benjamin A. Raby
- Channing Division of Network Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
- Scott T. Weiss
- Channing Division of Network Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
- Susetta Finotto
- Department of Molecular Pneumology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany; Corresponding author
- Journal volume & issue
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Vol. 24,
no. 10
p. 103163
Abstract
Summary: RANTES is implicated in allergic asthma and in T cell-dependent clearance of infection. RANTES receptor family comprises CCR1, CCR3, and CCR5, which are G-protein-coupled receptors consisting of seven transmembrane helices. Infections with respiratory viruses like Rhinovirus cause induction of RANTES production by epithelial cells. Here, we studied the role of RANTES in the peripheral blood mononuclear cells in cohorts of children with and without asthma and validated and extended this study to the airways of adults with and without asthma. We further translated these studies to a murine model of asthma induced by house dust mite allergen 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 of effector GATA-3+CD4+ T cells into immune-regulatory-type T cells and inflammatory eosinophils into resident eosinophils as well as increased IL-10 production in the lung.
