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)
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.
Impact Factor
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
Innate Lymphoid-cells; Pediatric Severe Asthma; Type-2 Immunity; Lung-function; Childhood; Inflammation; Activation; Children; Outcomes; Responsiveness
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2018
Prepublished im Jahr
HGF-Berichtsjahr
2018
ISSN (print) / ISBN
2470-9468
e-ISSN
2470-9468
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 3,
Heft: 27,
Seiten: ,
Artikelnummer: eaan4128
Supplement: ,
Reihe
Verlag
American Association for the Advancement of Science (AAAS)
Verlagsort
Washington, DC
Tag d. mündl. Prüfung
0000-00-00
Betreuer
Gutachter
Prüfer
Topic
Hochschule
Hochschulort
Fakultät
Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Asthma and Allergy Prevention (IAP)
POF Topic(s)
30202 - Environmental Health
Forschungsfeld(er)
Allergy
PSP-Element(e)
G-503300-001
Förderungen
Copyright
Erfassungsdatum
2018-09-20