Αρχειοθήκη ιστολογίου

Αλέξανδρος Γ. Σφακιανάκης
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5
Άγιος Νικόλαος Κρήτη 72100
2841026182
6032607174

Πέμπτη 7 Σεπτεμβρίου 2017

TNFAIP3 levels in lung dendritic cells instruct Th2 or Th17 cell differentiation in eosinophilic or neutrophilic asthma

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Publication date: Available online 6 September 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Heleen Vroman, Ingird M. Bergen, Jennifer .A.C. van Hulst, Memno van Nimwegen, Denise van Uden, Martin J. Schuijs, Saravanan Y. Pillai, Geert van Loo, Hamida Hammad, Bart N. Lambrecht, Rudi W. Hendriks, Mirjam Kool
BackgroundIt is currently unknown, why allergen exposure or environmental triggers in mild to moderate asthma patients results in Th2-mediated eosinophilic inflammation, whereas severe asthma patients often present with Th17-mediated neutrophilic inflammation. The activation state of dendritic cells (DCs) is crucial for both Th2 and Th17-cell differentiation, and is mediated through NF-κB activation. Ablation of TNFAIP3, one of the crucial negative regulators of NF-κB activation in myeloid cells and DCs was shown to control DC activation.ObjectiveIn this study we investigated the precise role of TNFAIP3 in myeloid cells for the development of Th2 and Th17-cell mediated asthma.MethodsWe exposed mice with conditional deletion of the Tnfaip3 gene in either myeloid cells (using the LysM promotor) or specifically in DCs (using the Cd11c promotor) to acute and chronic house dust mite (HDM)-driven asthma models.ResultsWe demonstrated that reduced Tnfaip3 gene expression in DCs in either Tnfaip3CD11c or Tnfaip3LysM mice dose-dependently controlled development of Th17-mediated neutrophilic severe asthma in both acute and chronic HDM-driven models, whereas wildtype mice developed a purely Th2-mediated eosinophilic inflammation. TNFAIP3-deficient DCs induced HDM-specific Th17-cell differentiation, through increased expression of Th17-instructing cytokines, IL-1ß, IL-6 and IL-23, whereas HDM-specific Th2-cell differentiation was hampered by the increased IL-12 and IL-6 production.ConclusionsThese data show that the extent of TNFAIP3 expression in DCs controls Th2/Th17-cell differentiation. This implies that reducing DC activation could be a new pharmacological intervention to treat severe asthma patients that present with a Th17-mediated neutrophilic inflammation.



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