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

(2018) CLINICAL AND EXPERIMENTAL ALLERGY. 48(12). p.1705-1714
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Organization
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-1β 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-1β and IL-6 that can, independently of IL-17-signalling, induce the expression of neutrophil chemo-attractants.
Keywords
asthma, IL-17A, neutrophils, MUCIN GENE-EXPRESSION, T-CELLS, ASTHMA, IL-17, RECEPTOR, INNATE, IL-22, HYPERRESPONSIVENESS, INTERLEUKIN-17, SENSITIZATION

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Chicago
Vroman, Heleen, Tridib Das, Ingrid M Bergen, Jennifer AC van Hulst, Fatemeh Ahmadi, Geert van Loo, Erik Lubberts, Rudi W Hendriks, and Mirjam Kool. 2018. “House Dust Mite-driven Neutrophilic Airway Inflammation in Mice with TNFAIP3-deficient Myeloid Cells Is IL-17-independent.” Clinical and Experimental Allergy 48 (12): 1705–1714.
APA
Vroman, H., Das, T., Bergen, I. M., van Hulst, J. A., Ahmadi, F., van Loo, G., Lubberts, E., et al. (2018). House dust mite-driven neutrophilic airway inflammation in mice with TNFAIP3-deficient myeloid cells is IL-17-independent. CLINICAL AND EXPERIMENTAL ALLERGY, 48(12), 1705–1714.
Vancouver
1.
Vroman H, Das T, Bergen IM, van Hulst JA, Ahmadi F, van Loo G, et al. House dust mite-driven neutrophilic airway inflammation in mice with TNFAIP3-deficient myeloid cells is IL-17-independent. CLINICAL AND EXPERIMENTAL ALLERGY. 2018;48(12):1705–14.
MLA
Vroman, Heleen et al. “House Dust Mite-driven Neutrophilic Airway Inflammation in Mice with TNFAIP3-deficient Myeloid Cells Is IL-17-independent.” CLINICAL AND EXPERIMENTAL ALLERGY 48.12 (2018): 1705–1714. Print.
@article{8581133,
  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-\ensuremath{\gamma} 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 \ensuremath{\gamma}\ensuremath{\delta}-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-1\ensuremath{\beta} 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-1\ensuremath{\beta} and IL-6 that can, independently of IL-17-signalling, induce the expression of neutrophil chemo-attractants.},
  author       = {Vroman, Heleen and Das, Tridib and Bergen, Ingrid M and van Hulst, Jennifer AC and Ahmadi, Fatemeh and van Loo, Geert and Lubberts, Erik and Hendriks, Rudi W and Kool, Mirjam},
  issn         = {0954-7894},
  journal      = {CLINICAL AND EXPERIMENTAL ALLERGY},
  language     = {eng},
  number       = {12},
  pages        = {1705--1714},
  title        = {House dust mite-driven neutrophilic airway inflammation in mice with TNFAIP3-deficient myeloid cells is IL-17-independent},
  url          = {http://dx.doi.org/10.1111/cea.13262},
  volume       = {48},
  year         = {2018},
}

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