Journal
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 140, Issue 4, Pages 1079-1089Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2016.11.046
Keywords
Allergic asthma; Notch signaling; Gata-3; T(H)2 immunity; T(H)1 immunity; house dust mite; Jagged; recombination signal-binding protein for immunoglobulin J(k) region; cytokines
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Funding
- Lung Foundation Netherlands [3.2.12.087, 3.2.12.067]
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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 Jk region (RBPJk), 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, RBPJk-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.
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