House dust mite-driven neutrophilic airway inflammation in mice with TNFAIP3-deficient myeloid cells is IL-17-independent

Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology
H VromanM Kool

Abstract

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. In this study, we investigated whether IL-17RA-signalling is essential for eosinophilic or neutrophilic inflammation in house dust mite (HDM)-driven airway inflammation. 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. 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...Continue Reading

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Citations

Dec 14, 2019·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·Graham RobertsJudith A Woodfolk
Dec 2, 2020·Biochemical and Biophysical Research Communications·Dong-Wook KwakJae-Hong Kim

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