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

doi:10.1016/j.isci.2021.103163

Regulated on Activation, Normal T cell Expressed and Secreted (RANTES) drives the resolution of allergic asthma

iScience. 2021 Sep 25;24(10):103163. doi: 10.1016/j.isci.2021.103163. eCollection 2021 Oct 22.

Authors

Nina Li¹, Hoomann Mirzakhani², Alexander Kiefer³, Julia Koelle¹, Tytti Vuorinen⁴, Manfred Rauh³, Zuqin Yang¹, Susanne Krammer¹, Paraskevi Xepapadaki⁵, Anna Lewandowska-Polak⁶, Heikki Lukkarinen⁷, Nan Zhang⁸, Barbara Stanic⁹, Theodor Zimmermann³, Marek L Kowalski¹⁰, Tuomas Jartti^{7

11

12}, Claus Bachert⁸, Mübeccel Akdis⁹, Nikolaos G Papadopoulos^{5

13}, Benjamin A Raby², Scott T Weiss², Susetta Finotto¹

Affiliations

¹ Department of Molecular Pneumology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany.
² Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
³ Department of Allergy and Pneumology, Children's Hospital, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany.
⁴ Medical Microbiology, Turku University Hospital, Institut of Biomedicine, University of Turku, Turku, Finland.
⁵ Department of Allergy, 2nd Pediatric Clinic, National and Kapodistrian University of Athens, Athens, Greece.
⁶ Department of Rheumatology, Medical University of Lodz, Lodz, Poland.
⁷ Department of Pediatrics and Adolescent Medicine, Turku University Hospital and University of Turku, Turku, Finland.
⁸ Upper Airways Research Laboratory, Otorhinolaryngology, University of Gent, Gent, Belgium.
⁹ Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Herman-Burchard-Strasse 9, Davos, Switzerland.
¹⁰ Department of Immunology and Allergy, Medical University of Lodz, Poland.
¹¹ PEDEGO Research Unit, Medical Research Center, University of Oulu, Oulu, Finland.
¹² Department of Pediatrics and Adolescent Medicine, Oulu University Hospital, Oulu, Finland.
¹³ Centre for Respiratory Medicine & Allergy, University of Manchester, Manchester, UK.

Abstract

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.

Keywords: Biological sciences; Immunology; Respiratory medicine.

Abstract

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