House dust mite-driven neutrophilic airway inflammation in mice with TNFAIP3-deficient myeloid cells is IL-17-independent.
Clin Exp Allergy
; 48(12): 1705-1714, 2018 12.
Article
en En
| MEDLINE
| ID: mdl-30171721
ABSTRACT
BACKGROUND:
Asthma is a heterogeneous disease of the airways that involves several types of granulocytic inflammation. Recently, we have shown that the activation status of myeloid cells regulated by TNFAIP3/A20 is a crucial determinant of eosinophilic or neutrophilic airway inflammation. However, whether neutrophilic inflammation observed in this model is dependent on IL-17 remains unknown.OBJECTIVE:
In this study, we investigated whether IL-17RA-signalling is essential for eosinophilic or neutrophilic inflammation in house dust mite (HDM)-driven airway inflammation.METHODS:
Tnfaip3fl/fl xLyz2+/cre (Tnfaip3LysM-KO ) mice were crossed to Il17raKO mice, generating Tnfaip3LysM Il17raKO mice and subjected to an HDM-driven airway inflammation model.RESULTS:
Both eosinophilic and neutrophilic inflammation observed in HDM-exposed WT and Tnfaip3LysM-KO mice respectively were unaltered in the absence of IL-17RA. Production of IL-5, IL-13 and IFN-γ by CD4+ T cells was similar between WT, Tnfaip3LysM-KO and Il17raKO mice, whereas mucus-producing cells in Tnfaip3LysM-KO Il17raKO mice were reduced compared to controls. Strikingly, spontaneous accumulation of pulmonary Th1, Th17 and γδ-17 T cells was observed in Tnfaip3LysM-KO Il17raKO mice, but not in the other genotypes. Th17 cell-associated cytokines such as GM-CSF and IL-22 were increased in the lungs of HDM-exposed Tnfaip3LysM-KO Il17raKO mice, compared to IL-17RA-sufficient controls. Moreover, neutrophilic chemo-attractants CXCL1, CXCL2, CXCL12 and Th17-promoting cytokines IL-1ß and IL-6 were unaltered between Tnfaip3LysM-KO and Tnfaip3LysM-KO Il17raKO mice. CONCLUSION AND CLINICAL RELEVANCE These findings show that neutrophilic airway inflammation induced by activated TNFAIP3/A20-deficient myeloid cells can develop in the absence of IL-17RA-signalling. Neutrophilic inflammation is likely maintained by similar quantities of pro-inflammatory cytokines IL-1ß and IL-6 that can, independently of IL-17-signalling, induce the expression of neutrophil chemo-attractants.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Asma
/
Interleucina-17
/
Células Mieloides
/
Pyroglyphidae
/
Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa
/
Neutrófilos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Clin Exp Allergy
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Países Bajos