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

活化调节正常T细胞表达和分泌因子(RANTES)驱动过敏性哮喘的消退

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作者: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

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.

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