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BMC Immunology
Published in: BMC Immunology 1/2021

Open Access 01-12-2021 | Bronchial Asthma | Research

PI3Kδ inhibition prevents IL33, ILC2s and inflammatory eosinophils in persistent airway inflammation

Authors: Sorif Uddin, Augustin Amour, David J. Lewis, Chris D. Edwards, Matthew G. Williamson, Simon Hall, Lisa A. Lione, Edith M. Hessel

Published in: BMC Immunology | Issue 1/2021

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Abstract

Background

Phosphoinositide-3-kinase-delta (PI3Kδ) inhibition is a promising therapeutic approach for inflammatory conditions due to its role in leucocyte proliferation, migration and activation. However, the effect of PI3Kδ inhibition on group 2 innate lymphoid cells (ILC2s) and inflammatory eosinophils remains unknown. Using a murine model exhibiting persistent airway inflammation we sought to understand the effect of PI3Kδ inhibition, montelukast and anti-IL5 antibody treatment on IL33 expression, group-2-innate lymphoid cells, inflammatory eosinophils, and goblet cell metaplasia.

Results

Mice were sensitised to house dust mite and after allowing inflammation to resolve, were re-challenged with house dust mite to re-initiate airway inflammation. ILC2s were found to persist in the airways following house dust mite sensitisation and after re-challenge their numbers increased further along with accumulation of inflammatory eosinophils. In contrast to montelukast or anti-IL5 antibody treatment, PI3Kδ inhibition ablated IL33 expression and prevented group-2-innate lymphoid cell accumulation. Only PI3Kδ inhibition and IL5 neutralization reduced the infiltration of inflammatory eosinophils. Moreover, PI3Kδ inhibition reduced goblet cell metaplasia.

Conclusions

Hence, we show that PI3Kδ inhibition dampens allergic inflammatory responses by ablating key cell types and cytokines involved in T-helper-2-driven inflammatory responses.
Appendix
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Metadata
Title
PI3Kδ inhibition prevents IL33, ILC2s and inflammatory eosinophils in persistent airway inflammation
Authors
Sorif Uddin
Augustin Amour
David J. Lewis
Chris D. Edwards
Matthew G. Williamson
Simon Hall
Lisa A. Lione
Edith M. Hessel
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Immunology / Issue 1/2021
Electronic ISSN: 1471-2172
DOI
https://doi.org/10.1186/s12865-021-00461-5

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