An evaluation of CD39 as a novel immunoregulatory mechanism invoked by COPD

Abstract

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are characterized by increased pulmonary and systemic inflammation and commonly caused by bacterial and/or viral infection. Little is known about the T-cell dysregulation in AECOPD that promotes these outcomes.CD39 is an ectonucleotidase able to hydrolyse adenosine triphosphate to create adenosine that may inhibit T-cell responses in patients with AECOPD. Here T-cell expression of CD39 measured by flow cytometry was higher in AECOPD patients than stable COPD patients or healthy controls. Higher expression of CD39 was associated with higher levels of plasma soluble tumor necrosis factor receptor but lower interferon-γ (IFNγ) levels in supernatants from staphylococcal enterotoxin-B stimulated peripheral blood mononuclear cells. This links increased expression of CD39 with systemic inflammation and impaired T-cell responses (e.g. IFNγ). The blockade of CD39 pathways may be a novel approach to the control of AECOPD, reducing the dependency on antibiotics.

Is the purinergic pathway involved in the pathology of COPD? Decreased lung CD39 expression at initial stages of COPD

“…The increased CD39 expression in leukocytes could compensate for the attenuated CD39 lung expression and combat airway inflammation in COPD. Tan D et al, [ 18 ] demonstrated enhanced expression of CD39 on circulating T-cell subsets in patients with an exacerbation of COPD compared with patients with stable COPD. Our results are not at odds with those of these two previous studies; in fact they complement our current knowledge of CD39 in COPD.…”

“…Our study did not analyze the expression of CD39 in the pulmonary or systemic inflammatory cells. However, the increase in CD39 expression in airway and systemic inflammatory cells suggested by both articles may be the compensatory mechanism for acute exposure to tobacco [ 17 ] or infection [ 18 ].…”

“…The role of CD39 in COPD has previously been investigated in an animal model of emphysema induced by tobacco exposure [ 17 ] and in inflammatory cells of COPD patients [ 17 , 18 ], but its expression in human lung tissue is unknown. To better understand the mechanisms underlying COPD pathology we compared CD39 expression and activity in the lungs of patients with COPD (COPD group), non-obstructed smokers (NOS group), and never smokers (NS group).…”

What Else Can CD39 Tell Us?

“…Consistent with the above results, CD39 expression and activity are elevated in chronic obstructive pulmonary disease (COPD) patients by quantifying CD39 expression and soluble ATPase activity in sputum and bronchoalveolar lavage fluid cells (98). Additionally, Tan et al showed T cell-related CD39 expression is higher in acute exacerbations of COPD (AECOPD) patients than stable COPD and healthy controls (5). They prospected blocking CD39 would be a novel approach to the control of AECOPD, reducing the dependency on antibiotics.…”

“…It is now again becoming a newly recognized “immune checkpoint mediator” that interferes with antitumor or anti-inflammatory immune response (5, 6). Moreover, some recent research has revealed a number of neoteric functions of CD39, which display its close relation with Tregs (7–9), Th17 cells (10, 11), γδ T cells (12), and Bregs (13).…”