Multi-Faceted Notch in Allergic Airway Inflammation
Abstract
:1. Introduction
1.1. Allergic Airway Diseases
1.2. Notch Signaling Pathway
1.3. Notch in Lung Development
2. Notch Signaling in Acute Allergic Airway Inflammation
2.1. Notch in Th Subset Differentiation and Immune Responses
2.2. Notch Ligand-Specific Allergic Immune Responses
2.3. Contradictory Findings
3. The Role of Notch Signaling in Chronic Allergic Airway Inflammation
3.1. Airway Remodeling and Angiogenesis in Chronic Asthma
3.2. Notch Signaling Family and Angiogenesis
3.3. Tregs Ameliorate Remodeling Angiogenesis by DLL4-Notch Signaling
4. Conclusions
Funding
Conflicts of Interest
References
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Delta-Like Ligand (DLL) | Jagged | γ-Secretase Inhibitor (GSI) |
---|---|---|
DLL4 was up-regulated on BMDCs after RSV infection. Anti-DLL4 Ab-treated animals developed substantially increased AHR [68]. | c-Kit-mutant mice had blunted Jagged2 expression on DCs and diminished Th2 & Th17 response to HDM allergic airway inflammation [62]. | IL-4-deficient recipients of GSI-treated naive CD4+ T cells developed lower levels of AHR, reduced numbers of eosinophils, and lower Th2 cytokine [52]. |
Treatment of OVA-sensitized and challenged mice with Delta1-Fc decreased AHR and airway inflammation [53]. | BMDCs pulsed with allergen upregulated the expression of Jagged1; transfer of these BMDCs induced AHR and eosinophilic airway inflammation. In vivo treatment with Jagged1-Fc enhanced AHR and airway inflammation [52]. | GSI-treated CD8+ T cells failed to restore OVA-induced airway inflammation and AHR in OVA-sensitized recipient CD8−/− mice [53]. |
DLL1 ligation endowed antigen-presenting cell functions on mast cells, with expression of MHC-II and OX40L and ability to promote naive CD4+ T cell proliferation and differentiation into Th2 cells [80]. | LPS-stimulated stromal cells induced upregulated expression of Jagged-1 by DCs, but not DLL4, which induced allergic airway inflammation [61]. | Administration of GSI inhibited asthma phenotypes, including eosinophilic airway inflammation, goblet cell metaplasia, AHR, and serum IgE [51]. |
DCs upregulated DLL4 expression in response to cockroach allergen. Blocking DLL4 in vivo enhanced allergen-induced AHR, Th2 cytokine production and mucus secretion [67]. | Jagged1 over-expression enhanced basal cell differentiation into secretory cells, but not ciliated cell differentiation [63]. | GSI treatment suppressed Th17 responses and ameliorated the development of OVA-induced allergic asthma [77]. |
Mouse mast cells adhered to DLL1-expressing stromal cells, suggesting Notch ligands provided an adhesion function, facilitating mast cell recruitment into inflammatory sites [81]. | Jagged1 inhibition mitigated Th2-dominated airway inflammation, whilst DLL4 blockage aggravated the asthma phenotypes due to impaired Treg induction. Adoptive transfer of DLL4-expressing antigen-presenting cells promoted Treg expansion [69]. | |
Anti-DLL4 Ab-treated mice had decreased Th17 cells and mitigated airway inflammation [78]. |
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Huang, M.-T.; Chiu, C.-J.; Chiang, B.-L. Multi-Faceted Notch in Allergic Airway Inflammation. Int. J. Mol. Sci. 2019, 20, 3508. https://doi.org/10.3390/ijms20143508
Huang M-T, Chiu C-J, Chiang B-L. Multi-Faceted Notch in Allergic Airway Inflammation. International Journal of Molecular Sciences. 2019; 20(14):3508. https://doi.org/10.3390/ijms20143508
Chicago/Turabian StyleHuang, Miao-Tzu, Chiao-Juno Chiu, and Bor-Luen Chiang. 2019. "Multi-Faceted Notch in Allergic Airway Inflammation" International Journal of Molecular Sciences 20, no. 14: 3508. https://doi.org/10.3390/ijms20143508
APA StyleHuang, M. -T., Chiu, C. -J., & Chiang, B. -L. (2019). Multi-Faceted Notch in Allergic Airway Inflammation. International Journal of Molecular Sciences, 20(14), 3508. https://doi.org/10.3390/ijms20143508