BLT1 signaling in epithelial cells mediates allergic sensitization via promotion of IL-33 production.
Allergens
/ immunology
Animals
Cytokines
/ metabolism
Epithelial Cells
/ metabolism
Hypersensitivity
/ genetics
Immunization
Interleukin-33
/ biosynthesis
Leukotriene B4
/ metabolism
Lymphocyte Activation
/ immunology
Lymphocytes
/ immunology
Mice
Papain
/ immunology
Proto-Oncogene Proteins c-akt
/ metabolism
Receptors, Leukotriene B4
/ metabolism
Signal Transduction
T-Lymphocyte Subsets
/ immunology
Journal
Allergy
ISSN: 1398-9995
Titre abrégé: Allergy
Pays: Denmark
ID NLM: 7804028
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
20
05
2018
revised:
11
10
2018
accepted:
22
10
2018
pubmed:
6
11
2018
medline:
18
4
2020
entrez:
4
11
2018
Statut:
ppublish
Résumé
Epithelial cells (ECs) play a crucial role in allergic sensitization to inhaled protease allergens by instructing type 2 innate lymphoid cells (ILC2) and dendritic cells (DCs) via release of pro-type 2 cytokines, particularly interleukin-33 (IL-33). Leukotriene B4 (LTB4) is a well-known leukocyte chemoattractant via engagement of its receptor 1 (BLT1). However, the role of LTB4-BLT1 axis in allergic sensitization via activation of ECs is still unknown. We evaluated the effect of LTB4-BLT1 axis on IL-33 expression and ILC2 activation in vivo and in vitro. Chimeric mice were established to evaluate the contribution of BLT1 expression in nonimmune cell to allergic sensitization. Genetical or pharmacological interruption of LTB4-BLT1 axis during sensitization phase markedly reduced papain-induced IL-33 expression, decreased ILC2 activation and DC migration, thereby impairing the priming of allergic Th2 responses. Furthermore, papain inhalation induced a rapid release of LTB4 preceding IL-33, and intranasal administration of LTB4 to naïve WT mice significantly increased IL-33 expression and ILC2 activation in lung, which was absent in Il33 Our study reveals a functional role of LTB4-BLT1 axis in nonimmune cells, most likely lung ECs, in controlling allergic sensitization as an upstream regulator of IL-33.
Sections du résumé
BACKGROUND
Epithelial cells (ECs) play a crucial role in allergic sensitization to inhaled protease allergens by instructing type 2 innate lymphoid cells (ILC2) and dendritic cells (DCs) via release of pro-type 2 cytokines, particularly interleukin-33 (IL-33). Leukotriene B4 (LTB4) is a well-known leukocyte chemoattractant via engagement of its receptor 1 (BLT1). However, the role of LTB4-BLT1 axis in allergic sensitization via activation of ECs is still unknown.
METHODS
We evaluated the effect of LTB4-BLT1 axis on IL-33 expression and ILC2 activation in vivo and in vitro. Chimeric mice were established to evaluate the contribution of BLT1 expression in nonimmune cell to allergic sensitization.
RESULTS
Genetical or pharmacological interruption of LTB4-BLT1 axis during sensitization phase markedly reduced papain-induced IL-33 expression, decreased ILC2 activation and DC migration, thereby impairing the priming of allergic Th2 responses. Furthermore, papain inhalation induced a rapid release of LTB4 preceding IL-33, and intranasal administration of LTB4 to naïve WT mice significantly increased IL-33 expression and ILC2 activation in lung, which was absent in Il33
CONCLUSION
Our study reveals a functional role of LTB4-BLT1 axis in nonimmune cells, most likely lung ECs, in controlling allergic sensitization as an upstream regulator of IL-33.
Substances chimiques
Allergens
0
Cytokines
0
Il33 protein, mouse
0
Interleukin-33
0
Ltb4r1 protein, mouse
0
Receptors, Leukotriene B4
0
Leukotriene B4
1HGW4DR56D
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Papain
EC 3.4.22.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
495-506Subventions
Organisme : National Natural Science Foundation of China Grant
ID : 81771202
Pays : International
Organisme : National Natural Science Foundation of China Grant
ID : 81771679
Pays : International
Organisme : National Natural Science Foundation of China Grant
ID : 81771784
Pays : International
Organisme : National Natural Science Foundation of China Grant
ID : 91642112
Pays : International
Organisme : State Key Basic Research Program (973) Project
ID : 2015CB553404
Pays : International
Informations de copyright
© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.