PI3Kδ inhibition prevents IL33, ILC2s and inflammatory eosinophils in persistent airway inflammation.
BMC Immunol
; 22(1): 78, 2021 12 17.
Article
in En
| MEDLINE
| ID: mdl-34920698
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Respiratory System
/
Lymphocytes
/
Eosinophils
/
Class I Phosphatidylinositol 3-Kinases
/
Interleukin-33
/
Hypersensitivity
/
Inflammation
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
BMC Immunol
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2021
Document type:
Article
Affiliation country:
United kingdom