We have located links that may give you full text access.
JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
TNF-α-induced protein 3 levels in lung dendritic cells instruct T H 2 or T H 17 cell differentiation in eosinophilic or neutrophilic asthma.
BACKGROUND: It is currently unknown why allergen exposure or environmental triggers in patients with mild-to-moderate asthma result in TH 2-mediated eosinophilic inflammation, whereas patients with severe asthma often present with TH 17-mediated neutrophilic inflammation. The activation state of dendritic cells (DCs) is crucial for both TH 2 and TH 17 cell differentiation and is mediated through nuclear factor κB activation. Ablation of TNF-α-induced protein 3 (TNFAIP3), one of the crucial negative regulators of nuclear factor κB activation in myeloid cells and DCs, was shown to control DC activation.
OBJECTIVE: In this study we investigated the precise role of TNFAIP3 in myeloid cells for the development of TH 2- and TH 17-cell mediated asthma.
METHODS: We exposed mice with conditional deletion of the Tnfaip3 gene in either myeloid cells (by using the lysozyme M [LysM] promotor) or specifically in DCs (by using the Cd11c promotor) to acute and chronic house dust mite (HDM)-driven asthma models.
RESULTS: We demonstrated that reduced Tnfaip3 gene expression in DCs in either Tnfaip3CD11c or Tnfaip3LysM mice dose-dependently controlled development of TH 17-mediated neutrophilic severe asthma in both acute and chronic HDM-driven models, whereas wild-type mice had a purely TH 2-mediated eosinophilic inflammation. TNFAIP3-deficient DCs induced HDM-specific TH 17 cell differentiation through increased expression of the TH 17-instructing cytokines IL-1β, IL-6, and IL-23, whereas HDM-specific TH 2 cell differentiation was hampered by increased IL-12 and IL-6 production.
CONCLUSIONS: These data show that the extent of TNFAIP3 expression in DCs controls TH 2/TH 17 cell differentiation. This implies that reducing DC activation could be a new pharmacologic intervention to treat patients with severe asthma who present with TH 17-mediated neutrophilic inflammation.
OBJECTIVE: In this study we investigated the precise role of TNFAIP3 in myeloid cells for the development of TH 2- and TH 17-cell mediated asthma.
METHODS: We exposed mice with conditional deletion of the Tnfaip3 gene in either myeloid cells (by using the lysozyme M [LysM] promotor) or specifically in DCs (by using the Cd11c promotor) to acute and chronic house dust mite (HDM)-driven asthma models.
RESULTS: We demonstrated that reduced Tnfaip3 gene expression in DCs in either Tnfaip3CD11c or Tnfaip3LysM mice dose-dependently controlled development of TH 17-mediated neutrophilic severe asthma in both acute and chronic HDM-driven models, whereas wild-type mice had a purely TH 2-mediated eosinophilic inflammation. TNFAIP3-deficient DCs induced HDM-specific TH 17 cell differentiation through increased expression of the TH 17-instructing cytokines IL-1β, IL-6, and IL-23, whereas HDM-specific TH 2 cell differentiation was hampered by increased IL-12 and IL-6 production.
CONCLUSIONS: These data show that the extent of TNFAIP3 expression in DCs controls TH 2/TH 17 cell differentiation. This implies that reducing DC activation could be a new pharmacologic intervention to treat patients with severe asthma who present with TH 17-mediated neutrophilic inflammation.
Full text links
Related Resources
Trending Papers
Heart failure with preserved ejection fraction: diagnosis, risk assessment, and treatment.Clinical Research in Cardiology : Official Journal of the German Cardiac Society 2024 April 12
Proximal versus distal diuretics in congestive heart failure.Nephrology, Dialysis, Transplantation 2024 Februrary 30
Efficacy and safety of pharmacotherapy in chronic insomnia: A review of clinical guidelines and case reports.Mental Health Clinician 2023 October
World Health Organization and International Consensus Classification of eosinophilic disorders: 2024 update on diagnosis, risk stratification, and management.American Journal of Hematology 2024 March 30
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app