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推动过敏性哮喘的消退。

drives the resolution of allergic asthma.

作者信息

Li Nina, Mirzakhani Hoomann, Kiefer Alexander, Koelle Julia, Vuorinen Tytti, Rauh Manfred, Yang Zuqin, Krammer Susanne, Xepapadaki Paraskevi, Lewandowska-Polak Anna, Lukkarinen Heikki, Zhang Nan, Stanic Barbara, Zimmermann Theodor, Kowalski Marek L, Jartti Tuomas, Bachert Claus, Akdis Mübeccel, Papadopoulos Nikolaos G, Raby Benjamin A, Weiss Scott T, Finotto Susetta

机构信息

Department of Molecular Pneumology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany.

Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

出版信息

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

DOI:10.1016/j.isci.2021.103163
PMID:34693221
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8511896/
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.

摘要

调节激活正常T细胞表达和分泌的因子（RANTES）与过敏性哮喘以及T细胞依赖性感染清除有关。RANTES受体家族包括CCR1、CCR3和CCR5，它们是由七个跨膜螺旋组成的G蛋白偶联受体。感染鼻病毒等呼吸道病毒会导致上皮细胞诱导RANTES的产生。在此，我们研究了RANTES在有或无哮喘儿童队列外周血单核细胞中的作用，并将该研究验证和扩展到有或无哮喘成人的气道。我们进一步将这些研究转化为在野生型RANTES和CCR5缺陷小鼠中由屋尘螨过敏原诱导的哮喘小鼠模型。我们在此表明，RANTES通过协调效应性GATA-3+CD4+T细胞向免疫调节型T细胞的转变、炎症性嗜酸性粒细胞向驻留嗜酸性粒细胞的转变以及肺中白细胞介素-10产生的增加，在变应原诱导的哮喘消退中发挥了意想不到的治疗作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd32/8511896/854ae73d73b5/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd32/8511896/dfb2287cc256/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd32/8511896/224fa217f69f/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd32/8511896/e5aa80d4e372/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd32/8511896/fd957d047928/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd32/8511896/d238491fce59/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd32/8511896/854ae73d73b5/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd32/8511896/dfb2287cc256/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd32/8511896/224fa217f69f/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd32/8511896/e5aa80d4e372/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd32/8511896/fd957d047928/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd32/8511896/d238491fce59/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd32/8511896/854ae73d73b5/gr5.jpg

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