Notch signaling in T cells is essential for allergic airway inflammation, but expression of the Notch ligands Jagged 1 and Jagged 2 on dendritic cells is dispensable.

Autor: Tindemans I; Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands., Lukkes M; Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands., de Bruijn MJW; Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands., Li BWS; Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands., van Nimwegen M; Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands., Amsen D; Sanquin, Amsterdam, The Netherlands., KleinJan A; Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands., Hendriks RW; Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands. Electronic address: r.hendriks@erasmusmc.nl.
Jazyk: angličtina
Zdroj: The Journal of allergy and clinical immunology [J Allergy Clin Immunol] 2017 Oct; Vol. 140 (4), pp. 1079-1089. Date of Electronic Publication: 2017 Jan 19.
DOI: 10.1016/j.jaci.2016.11.046
Abstrakt: Background: Allergic asthma is characterized by a T H 2 response induced by dendritic cells (DCs) that present inhaled allergen. Although the mechanisms by which they instruct T H 2 differentiation are still poorly understood, expression of the Notch ligand Jagged on DCs has been implicated in this process.
Objective: We sought to establish whether Notch signaling induced by DCs is critical for house dust mite (HDM)-driven allergic airway inflammation (AAI) in vivo.
Methods: The induction of Notch ligand expression on DC subsets by HDM was quantified by using quantitative real-time PCR. We used an HDM-driven asthma mouse model to compare the capacity of Jagged 1 and Jagged 2 single- and double-deficient DCs to induce AAI. In addition, we studied AAI in mice with a T cell-specific deletion of recombination signal-binding protein for immunoglobulin Jκ region (RBPJκ), a downstream effector of Notch signaling.
Results: HDM exposure promoted expression of Jagged 1, but not Jagged 2, on DCs. In agreement with published findings, in vitro-differentiated and HDM-pulsed Jagged 1 and Jagged 2 double-deficient DCs lacked the capacity to induce AAI. However, after in vivo intranasal sensitization and challenge with HDM, DC-specific Jagged 1 or Jagged 2 single- or double-deficient mice had eosinophilic airway inflammation and a T H 2 cell activation phenotype that was not different from that in control littermates. In contrast, RBPJκ-deficient mice did not experience AAI and airway hyperreactivity.
Conclusion: Our results show that the Notch signaling pathway in T cells is crucial for the induction of T H 2-mediated AAI in an HDM-driven asthma model but that expression of Jagged 1 or Jagged 2 on DCs is not required.
(Copyright © 2017. Published by Elsevier Inc.)
Databáze: MEDLINE
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