Attenuated allergic airway inflammation in Cd39-/- mice

Idzko, Marco; Ayata, K; Müller, Tobias; Dürk, Thorsten; Grimm, Melanie; Baudiß, K; Vieira, RP; Cicko, Sanja; Zech, Andreas; Sorichter, Stephan; Pelletier, Julie; Sévigny, Jean; Robson, Simon C.

doi:10.1055/s-0033-1334687

Cited by 2 publications

(7 citation statements)

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“…Indeed, allergic airway inflammation is associated with a decrease in pulmonary CD39 expression [14]. Surprisingly, we found an increase in CD39 expression of inflammatory cells and soluble ATPase activity in the airways of smokers and patients with COPD.…”

Section: Discussionmentioning

confidence: 50%

“…Interestingly, CD39 deficiency has been linked to both decreased (e.g. allergic airway inflammation) and increased airway inflammation (such as in LPS-induced acute lung injury) [14,20]. Here we demonstrate that expressions of cellular CD39 (on BALF and sputum cells) as well as the activity of the soluble ectonucleotidase are elevated in the airways of patients with COPD.…”

Section: Discussionmentioning

confidence: 55%

“…Besides inflammatory cells, pulmonary ATP concentration is also controlled by CD39 strongly expressed on airway epithelial cells [14]. Therefore, we further assessed the expression and pulmonary activity of membrane-bound ATPase in lung tissue of mice exposed to cigarette smoke for up to 28 days.…”

Section: Resultsmentioning

confidence: 99%

“…) on a C57BL/6 background were generated as previously described [14]. All experiments were performed according to institutional guidelines of the animal ethics committees of the Italian or German governments.…”

Section: Methodsmentioning

confidence: 99%

“…Consequently, an important role of CD39 in inflammatory disorders, including acute respiratory distress syndrome, hyperoxic acute lung injury, colitis and autoimmune diabetes has been demonstrated [12,13]. Recently, we have shown that CD39 is involved in the pathogenesis of allergic airway inflammation by modulating dendritic cell function [14]. However, the role and regulation of CD39 in the development and maintenance of cigarette smoke-induced lung inflammation and emphysema is unknown.…”

Section: Introductionmentioning

confidence: 99%

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NTPDase1/CD39 and aberrant purinergic signalling in the pathogenesis of COPD

et al. 2015

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Purinergic receptor activation via extracellular ATP is involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Nucleoside triphosphate diphosphohydrolase-1/CD39 hydrolyses extracellular ATP and modulates P2 receptor signalling.We aimed to investigate the expression and function of CD39 in the pathogenesis of cigarette smokeinduced lung inflammation in patients and preclinical mouse models. CD39 expression and soluble ATPase activity were quantified in sputum and bronchoalveolar lavage fluid (BALF) cells in nonsmokers, smokers and COPD patients or mice with cigarette smoke-induced lung inflammation. In mice, pulmonary ATP and cytokine concentrations, inflammation and emphysema were analysed in the presence or absence of CD39.Following acute cigarette smoke exposure CD39 was upregulated in BALF cells in smokers with further increases in COPD patients. Acute cigarette smoke exposure induced CD39 upregulation in murine lungs and BALF cells, and ATP degradation was accelerated in airway fluids. CD39 inhibition and deficiency led to augmented lung inflammation; treatment with ATPase during cigarette smoke exposure prevented emphysema.Pulmonary CD39 expression and activity are increased in COPD. CD39 deficiency leads to enhanced emphysema in mice, while external administration of a functional CD39 analogue partially rescues the phenotype. The compensatory upregulation of pulmonary CD39 might serve as a protective mechanism in cigarette smoke-induced lung damage. @ERSpublications The upregulation of pulmonary ATPase is a protective mechanism in cigarette smoke-induced lung inflammation http://ow.ly/S5YcC

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Section: Discussionmentioning

confidence: 50%

Section: Discussionmentioning

confidence: 55%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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NTPDase1/CD39 and aberrant purinergic signalling in the pathogenesis of COPD

et al. 2015

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Epithelial microRNA-206 targets CD39/extracellular ATP to upregulate airway IL-25 and TSLP in type 2-high asthma

et al. 2021

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The epithelial cell-derived cytokines IL-25, IL-33 and TSLP initiate type inflammation in allergic diseases including asthma. However, the signaling pathway regulating these cytokines expression remains elusive. Since microRNAs are pivotal regulators of gene expression, we profiled microRNA expression in bronchial epithelial brushings from type 2-low and type 2-high asthma patients. MiR-206 was the most highly expressed epithelial microRNA in type 2-high asthma relative to type 2-low asthma but was downregulated in both subsets compared with healthy controls. CD39, an ectonucleotidase degrading ATP, was a target of miR-206 and upregulated in asthma. Allergen-induced acute extracellular ATP accumulation led to miR-206 downregulation and CD39 upregulation in human bronchial epithelial cells, forming a feedback loop to eliminate excessive ATP. Airway ATP levels were markedly elevated and strongly correlated with IL-25 and TSLP expression in asthma patients. Intriguingly, airway miR-206 antagonism increased Cd39 expression, reduced ATP accumulation, suppressed Il-25, Il-33, Tslp expression and group 2 innate lymphoid cell expansion, and alleviated type 2 inflammation in a mouse model of allergic airway inflammation. In contrast, airway miR-206 overexpression had opposite effects. Overall, epithelial miR-206 upregulates airway IL-25, TSLP expression by targeting CD39-extracellular ATP axis, which represents a novel therapeutic target in type 2-high asthma.

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Attenuated allergic airway inflammation in Cd39-/- mice

Cited by 2 publications

References 0 publications

NTPDase1/CD39 and aberrant purinergic signalling in the pathogenesis of COPD

NTPDase1/CD39 and aberrant purinergic signalling in the pathogenesis of COPD

Epithelial microRNA-206 targets CD39/extracellular ATP to upregulate airway IL-25 and TSLP in type 2-high asthma

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