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

Title: Inception of early life allergen induced airway hyperresponsiveness is reliant on IL-13+CD4+ T cells
Authors: Saglani, S
Item 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.
Issue Date: 7-Sep-2018
Date of Acceptance: 9-Jul-2018
URI: http://hdl.handle.net/10044/1/62361
DOI: https://dx.doi.org/10.1126/sciimmunol.aan4128
ISSN: 2470-9468
Publisher: American Association for the Advancement of Science
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
Publication Status: Published
Online Publication Date: 2018-09-07
Appears in Collections:National Heart and Lung Institute
Faculty of Medicine



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