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

Tindemans, Irma; Lukkes, Melanie; Bruijn, Marjolein J. W. de; Li, Bobby W. S.; Nimwegen, Menno van; Amsen, Derk; KleinJan, Alex; Hendriks, Rudi W.

doi:10.1016/j.jaci.2016.11.046

Cited by 32 publications

(37 citation statements)

References 37 publications

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“…Notch signaling is essential for cellular growth and regulation. When completely knocked out, it is embryonically lethal [6, 7]. Studies have confirmed that Notch signaling is widely involved in the development and differentiation of T cells and is closely related to a number of diseases of the immune system.…”

Section: Introductionmentioning

confidence: 99%

Notch Signaling Promotes Development of Allergic Rhinitis by Suppressing Foxp3 Expression and Treg Cell Differentiation

Jiao

Wei

Kong

et al. 2018

Int Arch Allergy Immunol

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Background: The Notch signaling pathway plays an important role in regulating human immune function, but the relationship between allergic rhinitis (AR) and Notch signaling remains unclear. Objective: To investigate the role of Notch signaling in the pathogenesis of AR and its regulation on Foxp3-Treg cells. Method: The sera of 100 patients with AR and 50 controls were collected to assess the differences in Notch1, Jagged1, and DLL1 (Delta-like 1) expression. Experimental mice were divided into normal control, AR, Notch inhibitor, and dexamethasone groups. Allergic symptoms, total IgE levels, and the proportion of Treg cells in the peripheral blood were detected. Notch1, Jagged1, NICD (Notch intracellular domain, also known as ICN), and Foxp3 expression and Th1/Th2/Th17-related cytokines in the spleen were detected and compared between each group of mice. Results: Compared with the control group, the expression of Notch1 and Jagged1 in patients with AR was significantly elevated (p < 0.05). The expression of Notch1 and Jagged1 in patients with severe AR was higher than that observed in the mild to moderate AR patients and positively correlated with the levels of allergen sIgE (p < 0.05). The animal experiments revealed that compared with the normal control group, the expression of Notch1, Jagged1, and NICD in the AR group was increased, Foxp3 expression was decreased, and the proportion of Treg cells was decreased (p < 0.05). Compared with the AR group, allergic symptoms and total serum IgE levels and the expression of Notch1, Jagged1, and NICD were significantly decreased in the Notch inhibited group, whereas the expression of Foxp3 and the proportion of Treg cells were increased significantly (p < 0.05). The Th2-type immune responses were also enhanced and Th1-type immune responses decreased in the AR group, but the Th1/Th2 imbalance was reversed in the Notch inhibited group. Conclusion: Notch signaling downregulates Foxp3 expression and inhibits the differentiation of Treg cells to promote the development of AR. Blocking Notch signaling may be a potential treatment for AR.

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Section: Introductionmentioning

confidence: 99%

Notch Signaling Promotes Development of Allergic Rhinitis by Suppressing Foxp3 Expression and Treg Cell Differentiation

Jiao

Wei

Kong

et al. 2018

Int Arch Allergy Immunol

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“…Therefore, it is attractive to speculate that endothelial cells are critical to provide Notch ligands, particularly since these cells have the capacity to upregulate Jagged expression in response to inflammatory mediators such as TNF and IL-6 (53,54). Accordingly, we found that HDM exposure in mice induced Jagged and DLL expression in MedLN endothelial cells ( Figure 7G) and that Jagged expression on DCs is not critical for HDM-driven allergic AAI in vivo (55).…”

Section: Preparation Of Single-cell Suspensionsmentioning

confidence: 85%

“…Single-cell suspensions were stained with a mixture of fluorochrome-labeled antibodies in FACS buffer containing 0.25% BSA, 0.5 mM EDTA, 0.05% NaN 3 in PBS (55,57). A list of all fluorochrome-labeled antibodies that were used can be found in Supplemental Table 1.…”

Section: Flow Cytometrymentioning

confidence: 99%

“…GM-CSF bone marrow-derived DCs were generated as previously described (55,62) and stimulated overnight with 5 μg/mL HDM or 100 ng/mL LPS (Enzo Life Sciences) in combination with variable concentrations of endotoxin-free OVA as indicated in the figure legends. Naive T cells were isolated from spleen and lymph nodes of OTII mice using a CD4 + T cell MACS isolation kit and were subsequently sorted using a FACSAria equipped with BD FACSDiva software (BD Biosciences), as described above.…”

Section: Dc-otii Cell Coculturesmentioning

confidence: 99%

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Notch signaling licenses allergic airway inflammation by promoting Th2 cell lymph node egress

Tindemans¹,

Schoonhoven²,

KleinJan³

et al. 2020

Journal of Clinical Investigation

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“…Notch 1 is thought to contribute to the development of asthma by contributing to the Th1/Th2 disbalance [27]. Given that glucocorticoids are the standard of care for allergic asthma, the effect of glucocorticoids on the Notch 1 pathway was also investigated in parallel.…”

Section: Asthmamentioning

confidence: 99%

Recent Advances in Experimental Allergy

Adams

Gunten

2018

Int Arch Allergy Immunol

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Atopic disorders are on the rise and pose a great burden on society. A better understanding of the underlying mechanisms is required for the development of improved or novel therapeutic strategies. Here we aim to highlight recent advances in experimental allergy, with a particular focus on proposed treatment alternatives for airway disorders, atopic dermatitis, and food allergy. Furthermore, we discuss recent work focusing on molecular and cellular mechanisms that might offer candidates for future preventive or therapeutic intervention.

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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

Abstract: Our results show that the Notch signaling pathway in T cells is crucial for the induction of T2-mediated AAI in an HDM-driven asthma model but that expression of Jagged 1 or Jagged 2 on DCs is not required.

Cited by 32 publications

References 37 publications

Notch Signaling Promotes Development of Allergic Rhinitis by Suppressing Foxp3 Expression and Treg Cell Differentiation

Notch Signaling Promotes Development of Allergic Rhinitis by Suppressing Foxp3 Expression and Treg Cell Differentiation

Notch signaling licenses allergic airway inflammation by promoting Th2 cell lymph node egress

Recent Advances in Experimental Allergy

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