University of Hertfordshire

From the same journal

By the same authors

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

Research output: Contribution to journalArticlepeer-review

Documents

  • Sorif Uddin
  • Augustin Amour
  • Chris D Edwards
  • Matthew G Williamson
  • Simon Hall
  • Lisa Lione
  • Edith M Hessel
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Original languageEnglish
Number of pages31
JournalBMC Immunology
DOIs
Publication statusAccepted/In press - 9 Mar 2021

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.

Notes

This is the preprint version of an article (currently under review at BMC Immunology) available at https://dx.doi.org/10.21203/rs.3.rs-209463/v1. This work is licensed under a Creative Commons Attribution 4.0 International License. https://creativecommons.org/licenses/by/4.0/.

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