Inception of early life allergen induced airway hyperresponsiveness is reliant on IL-13+CD4+ T cells
Author(s)
Type
Journal Article
Abstract
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 LinnegCD45+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 CD4creIL-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 CD4creIL-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.
Date Issued
2018-09-14
Date Acceptance
2018-07-09
Citation
Science Immunology, 2018, 3 (27), pp.1-12
ISSN
2470-9468
Publisher
American Association for the Advancement of Science
Start Page
1
End Page
12
Journal / Book Title
Science Immunology
Volume
3
Issue
27
Copyright Statement
© 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. This is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science Immunology Volume 3, Issue 27, 7th Sept 2018, DOI: 10.1126/sciimmunol.aan4128
Sponsor
Wellcome Trust
Wellcome Trust
Wellcome Trust
Grant Number
083586/Z/07/Z
083586/Z/07/Z
107059/Z/15/Z
Subjects
Science & Technology
Life Sciences & Biomedicine
Immunology
INNATE LYMPHOID-CELLS
PEDIATRIC SEVERE ASTHMA
TYPE-2 IMMUNITY
LUNG-FUNCTION
ACTIVATION
CHILDHOOD
OUTCOMES
RESPONSIVENESS
RESPONSES
CHILDREN
Acinetobacter
Allergens
Alternaria
Animals
Animals, Newborn
CD4-Positive T-Lymphocytes
Female
Interleukin-13
Interleukin-33
Male
Mice, Inbred BALB C
Mice, Knockout
Mice, SCID
Pyroglyphidae
Respiratory Hypersensitivity
CD4-Positive T-Lymphocytes
Animals
Mice, Inbred BALB C
Animals, Newborn
Mice, Knockout
Mice, SCID
Pyroglyphidae
Acinetobacter
Alternaria
Respiratory Hypersensitivity
Interleukin-13
Allergens
Female
Male
Interleukin-33
Publication Status
Published
Date Publish Online
2018-09-07