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    CD73+ regulatory T cells contribute to adenosine-mediated resolution of acute lung injury

    Ehrentraut, Heidi and Clambey, Eric T. and McNamee, Eóin N. and Brodsky, Kelley S. and Ehrentraut, Stefan F. and Poth, Jens M. and Riegel, Ann K. and Westrich, Joseph A. and Colgan, S.P. and Eltzschig, Holger K. (2013) CD73+ regulatory T cells contribute to adenosine-mediated resolution of acute lung injury. FASEB Journal, 27 (6). pp. 2207-2219. ISSN 1530-6860

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    Acute lung injury (ALI) is characterized by alveolar injury and uncontrolled inflammation. Since most cases of ALI resolve spontaneously, understanding the endogenous mechanisms that promote ALI resolution is important to developing effective therapies. Previous studies have implicated extracellular adenosine signaling in tissue adaptation and wound healing. Therefore, we hypothesized a functional contribution for the endogenous production of adenosine during ALI resolution. As a model, we administered intratracheal LPS and observed peak lung injury at 3 d, with resolution by d 14. Treatment with pegylated adenosine-deaminase to enhance extracellular adenosine breakdown revealed impaired ALI resolution. Similarly, genetic deletion of cd73, the pacemaker for extracellular adenosine generation, was associated with increased mortality (0% wild-type and 40% in cd73/ mice; P<0.05) and failure to resolve ALI adequately. Studies of inflammatory cell trafficking into the lungs during ALI resolution revealed that regulatory T cells (Tregs) express the highest levels of CD73. While Treg numbers in cd73/ mice were similar to controls, cd73-deficient Tregs had attenuated immunosuppressive functions. Moreover, adoptive transfer of cd73- deficient Tregs into Rag/ mice emulated the observed phenotype in cd73/ mice, while transfer of wild-type Tregs was associated with normal ALI resolution. Together, these studies implicate CD73-dependent adenosine generation in Tregs in promoting ALI resolution.

    Item Type: Article
    Keywords: ectonucleotidase; lipopolysaccharide; hypoxia; Adora2b; inflammation;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 12583
    Identification Number:
    Depositing User: Eoin McNamee
    Date Deposited: 20 Mar 2020 11:16
    Journal or Publication Title: FASEB Journal
    Publisher: Federation of American Society of Experimental Biology
    Refereed: Yes
    Use Licence: This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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