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Saglani, S.* ; Gregory, L.G.* ; Manghera, A.K.* ; Branchett, W.J.* ; Uwadiae, F.* ; Entwistle, L.J.* ; Oliver, R.A.* ; Vasiliou, J.E.* ; Sherburn, R.* ; Lui, S.* ; Puttur, F.* ; Vöhringer, D.* ; Walker, S.A.* ; Buckley, J.* ; Grychtol, R.* ; Fainardi, V.* ; Denney, L.* ; Byrne, A.* ; von Mutius, E. ; Bush, A.* ; Lloyd, C.M.*

Inception of early-life allergen-induced airway hyperresponsiveness is reliant on IL-13+CD4+ T cells.

Sci. Immunol. 3:eaan4128 (2018)
Postprint DOI PMC
Open Access Green
Airway hyperresponsiveness (AHR) is a critical feature of wheezing and asthma in children, but the initiating immune mechanisms remain unconfirmed. We demonstrate that both recombinant interleukin-33 (rIL-33) and allergen [ house dust mite (HDM) or Alternaria alternata] exposure from day 3 of life resulted in significantly increased pulmonary IL-13(+)CD4(+) T cells, which were indispensable for the development of AHR. In contrast, adult mice had a predominance of pulmonary Lin(neg)CD45(+)CD90(+)IL-13(+) type 2 innate lymphoid cells (ILC2s) after administration of rIL-33. HDM exposure of neonatal IL-33 knockout (KO) mice still resulted in AHR. However, neonatal CD4(cre)IL-13 KO mice (lacking IL-13(+)CD4(+) T cells) exposed to allergen from day 3 of life were protected from AHR despite persistent pulmonary eosinophilia, elevated IL-33 levels, and IL-13(+) ILCs. Moreover, neonatal mice were protected from AHR when inhaled Acinetobacter lwoffii (an environmental bacterial isolate found in cattle farms, which is known to protect from childhood asthma) was administered concurrent with HDM. A. lwoffii blocked the expansion of pulmonary IL-13(+)CD4(+) T cells, whereas IL-13(+) ILCs and IL-33 remained elevated. Administration of A. lwoffii mirrored the findings from the CD4(cre)IL-13 KO mice, providing a translational approach for disease protection in early life. These data demonstrate that IL-13(+)CD4(+) T cells, rather than IL-13(+) ILCs or IL-33, are critical for inception of allergic AHR in early life.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Innate Lymphoid-cells; Pediatric Severe Asthma; Type-2 Immunity; Lung-function; Childhood; Inflammation; Activation; Children; Outcomes; Responsiveness
Language english
Publication Year 2018
HGF-reported in Year 2018
ISSN (print) / ISBN 2470-9468
e-ISSN 2470-9468
Journal Science immunology
Quellenangaben Volume: 3, Issue: 27, Pages: , Article Number: eaan4128 Supplement: ,
Publisher American Association for the Advancement of Science (AAAS)
Publishing Place Washington, DC
Reviewing status Peer reviewed
Institute(s) Institute of Asthma and Allergy Prevention (IAP)
POF-Topic(s) 30202 - Environmental Health
Research field(s) Allergy
PSP Element(s) G-503300-001
DOI 10.1126/sciimmunol.aan4128
WOS ID WOS:000446546600005
PubMed ID 30194239
Erfassungsdatum 2018-09-20
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