Multi-Faceted Notch in Allergic Airway Inflammation

Abstract

Notch is an evolutionarily conserved signaling family which iteratively exerts pleiotropic functions in cell fate decisions and various physiological processes, not only during embryonic development but also throughout adult life. In the context of the respiratory system, Notch has been shown to regulate ciliated versus secretory lineage differentiation of epithelial progenitor cells and coordinate morphogenesis of the developing lung. Reminiscent of its role in development, the Notch signaling pathway also plays a role in repair of lung injuries by regulation of stem cell activity, cell differentiation, cell proliferation and apoptosis. In addition to functions in embryonic development, cell and tissue renewal and various physiological processes, including glucose and lipid metabolism, Notch signaling has been demonstrated to regulate differentiation of literally almost all T-cell subsets, and impact on elicitation of inflammatory response and its outcome. We have investigated the role of Notch in allergic airway inflammation in both acute and chronic settings. In this mini-review, we will summarize our own work and recent advances on the role of Notch signaling in allergic airway inflammation, and discuss potential applications of the Notch signaling family in therapy for allergic airway diseases.

EVs from BALF—Mediators of Inflammation and Potential Biomarkers in Lung Diseases

“…Allergic airway inflammation is a condition characterized by IgE-dependent mast-cell activation, eosinophilic infiltration, and Th2 lymphocyte migration to the airway mucosa [ 70 ]. IL-4 and IL-13 are the main cytokines associated with allergic inflammation [ 71 ].…”

Asthma in the Precision Medicine Era: Biologics and Probiotics

“…The cause of neutrophilic inflammation in Th2-low asthma is still unclear. The nature of the inciting agents/allergens and the immediate downstream signaling pathways as elicited by the inciting agents, such as differential Notch receptor-ligand pair signaling, are tentative regulators for Th2-low inflammation [ 42 , 43 ]. Nonetheless, the off-target effect of high-dose corticosteroid on neutrophilia and the masking of eosinophilic inflammation by steroid therapy should be taken into consideration in Th2-low asthma presented as neutrophilic inflammation.…”

Obesity and asthma

“…The Notch signaling pathway is known to be on the one hand important in the allergic airway inflammation, but on the other hand Notch signaling is also able to regulate metabolism. 45,46 Therefore, the y-secretase inhibitors, which are blocking the Notch signaling pathways, might be an effective treatment, leading to a decrease in the T H 17 response and alleviated AHR in y-secretase inhibitor-treated HFD/OVA mice. 47 Moreover, weight loss or bariatric surgery can lead to improvements in disease control.…”