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
Abstract
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: |
https://doi.org/10.1096/fj.12-225201 |
| 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 |
| URI: |
|
| 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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