Exploring the role of Coxsackie and Adenovirus Receptor (CAR) in allergic airway inflammation

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.

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Role of Interleukin-25 in allergic airway inflammation and vascular damage

Inflammation and Regeneration ◽

10.2492/inflammregen.31.420 ◽

2011 ◽

Vol 31 (5) ◽

pp. 420-424

Author(s):

Hiroshi Nakajima ◽

Saki Kawashima ◽

Tomohiro Tamachi ◽

Kentaro Takahashi ◽

Koichi Hirose

Keyword(s):

Airway Inflammation ◽

Allergic Airway Inflammation ◽

Vascular Damage ◽

Interleukin 25

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HDAC2 attenuates airway inflammation by suppressing IL-17A production in HDM-challenged mice

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00143.2018 ◽

2019 ◽

Vol 316 (1) ◽

pp. L269-L279 ◽

Cited By ~ 4

Author(s):

Tianwen Lai ◽

Mindan Wu ◽

Chao Zhang ◽

Luanqing Che ◽

Feng Xu ◽

...

Keyword(s):

Airway Inflammation ◽

Inflammatory Cytokines ◽

Allergic Inflammation ◽

Allergic Airway Inflammation ◽

Inflammatory Cells ◽

Protective Role ◽

In Vivo Models

Histone deacetylase (HDAC)2 is expressed in airway epithelium and plays a pivotal role in inflammatory cells. However, the role of HDAC2 in allergic airway inflammation remains poorly understood. In the present study, we determined the role of HDAC2 in airway inflammation using in vivo models of house dust mite (HDM)-induced allergic inflammation and in vitro cultures of human bronchial epithelial (HBE) cells exposed to HDM, IL-17A, or both. We observed that HDM-challenged Hdac2+/− mice exhibited substantially enhanced infiltration of inflammatory cells. Higher levels of T helper 2 cytokines and IL-17A expression were found in lung tissues of HDM-challenged Hdac2+/− mice. Interestingly, IL-17A deletion or anti-IL-17A treatment reversed the enhanced airway inflammation induced by HDAC2 impairment. In vitro, HDM and IL-17A synergistically decreased HDAC2 expression in HBE cells. HDAC2 gene silencing further enhanced HDM- and/or IL-17A-induced inflammatory cytokines in HBE cells. HDAC2 overexpresion or blocking IL-17A gene expression restored the enhanced inflammatory cytokines. Collectively, these results support a protective role of HDAC2 in HDM-induced airway inflammation by suppressing IL-17A production and might suggest that activation of HDAC2 and/or inhibition of IL-17A production could prevent the development of allergic airway inflammation.

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Exacerbation of Allergic Airway Inflammation in Mice Lacking ECTO-5′-Nucleotidase (CD73)

Frontiers in Pharmacology ◽

10.3389/fphar.2020.589343 ◽

2020 ◽

Vol 11 ◽

Author(s):

Elisabetta Caiazzo ◽

Ida Cerqua ◽

Maria Antonietta Riemma ◽

Roberta Turiello ◽

Armando Ialenti ◽

...

Keyword(s):

Airway Inflammation ◽

Allergic Sensitization ◽

Adaptive Immune Response ◽

Allergic Airway Inflammation ◽

Individual Response ◽

Type I ◽

Target Tissue ◽

Extracellular Adenosine ◽

Reduced Frequency

The airways are a target tissue of type I allergies and atopy is the main etiological factor of bronchial asthma. A predisposition to allergy and individual response to allergens are dependent upon environmental and host factors. Early studies performed to clarify the role of extracellular adenosine in the airways highlighted the importance of adenosine-generating enzymes CD73, together with CD39, as an innate protection system against lung injury. In experimental animals, deletion of CD73 has been associated with immune and autoimmune diseases. Our experiments have been performed to investigate the role of CD73 in the assessment of allergic airway inflammation following sensitization. We found that in CD73−/− mice sensitization, induced by subcutaneous ovalbumin (OVA) administration, increased signs of airway inflammation and atopy developed, characterized by high IgE plasma levels and increased pulmonary cytokines, reduced frequency of lung CD4+CD25+Foxp3+ T cells, but without bronchial hyperreactivity, compared to sensitized wild type mice. Our results provide evidence that the lack of CD73 causes an uncontrolled allergic sensitization, suggesting that CD73 is a key molecule at the interface between innate and adaptive immune response. The knowledge of host immune factors controlling allergic sensitization is of crucial importance and might help to find preventive interventions that could act before an allergy develops.

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