Pulmonary type2 innate lymphoid cells in paediatric severe asthma: phenotype and response to steroids

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Title: Pulmonary type2 innate lymphoid cells in paediatric severe asthma: phenotype and response to steroids
Authors: Nagakumar, P
Puttur, F
Gregory, LG
Denney, L
Fleming, L
Bush, A
Lloyd, CM
Saglani, S
Item Type: Journal Article
Abstract: Children with severe therapy resistant asthma (STRA) have poor control despite maximal treatment, while those with difficult asthma (DA) have poor control from failure to implement basic management including adherence to therapy. Although recognised as clinically distinct, the airway molecular phenotype, including the role of ILCs and their response to steroids in DA and STRA is unknown.Immunophenotyping of sputum and blood ILCs and T cells from STRA, DA and non-asthmatic controls was undertaken. Leukocytes were analysed longitudinally pre and post intramuscular triamcinolone in children with STRA. Cultured ILCs were also evaluated to assess steroid responsiveness in vitroAirway eosinophils, Th2 cells and ILC2s were significantly higher in STRA patients compared to DA and disease controls, while IL-17+ lymphoid cells were similar. ILC2s and Th2 cells were significantly reduced in vivo following intramuscular triamcinolone and in vitro with steroids. Asthma attacks and symptoms also reduced after systemic steroids despite persistence of steroid resistant IL-17+ cells and eosinophils.Paediatric STRA and DA have distinct airway molecular phenotypes with STRA characterised by elevated type2 cells. Systemic corticosteroids but not maintenance inhaled steroids resulted in improved symptom control and exacerbations concomitant with a reduction in functional ILC2s despite persistently elevated IL-17+ lymphoid cells.
Issue Date: 4-Jun-2019
Date of Acceptance: 27-May-2019
URI: http://hdl.handle.net/10044/1/70799
DOI: https://doi.org/10.1183/13993003.01809-2018
ISSN: 0903-1936
Publisher: European Respiratory Society
Journal / Book Title: European Respiratory Journal
Copyright Statement: © 2019 ERS.
Sponsor/Funder: Wellcome Trust
Funder's Grant Number: 087618/Z/08/Z
Keywords: Respiratory System
11 Medical and Health Sciences
Publication Status: Published online
Conference Place: England
Embargo Date: 2020-06-04
Online Publication Date: 2019-06-04
Appears in Collections:National Heart and Lung Institute



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