CD73 is expressed by inflammatory Th17 cells in experimental autoimmune encephalomyelitis but does not limit differentiation or pathogenesis
Author(s)
Hernandez Mir, G
McGeachy, MJ
Type
Journal Article
Abstract
CD73 works together with CD39 to convert extracellular ATP to immunoregulatory adenosine,
thus inhibiting inflammation. TGFβ-mediated CD73 expression on ‘regulatory’ Th17
cells limits their ability to eradicate tumors, similar to the immunosuppressive mechanism
described for CD73 on Tregs. However, CD73 is also expressed on Th17 cells thought to be
inflammatory in Crohn’s disease. CD73 has previously been reported to contribute to inflammation
in the central nervous system (CNS). In experimental autoimmune encephalomyelitis
(EAE), we found that inflammatory cytokine-producing Th17 cells showed increased
CD73 expression as disease progressed. We therefore hypothesized that CD73 could be
important for limiting the expansion or pathogenic function of Th17 cells in autoimmune
inflammation of the CNS. Surprisingly, EAE development was not enhanced or inhibited by
CD73 deficiency; there was correspondingly no difference in induction of Th17-associated
cytokines IL-17, IFNγ or GM-CSF or recruitment of either inflammatory or regulatory cells to
the central nervous system. We confirmed that CD73 was similarly not required for differentiation
of Th17 cells in vitro. These data show that while CD73 expression is regulated during
EAE, this enzyme is not absolutely required to either promote or limit Th17 cell expansion or
EAE severity
thus inhibiting inflammation. TGFβ-mediated CD73 expression on ‘regulatory’ Th17
cells limits their ability to eradicate tumors, similar to the immunosuppressive mechanism
described for CD73 on Tregs. However, CD73 is also expressed on Th17 cells thought to be
inflammatory in Crohn’s disease. CD73 has previously been reported to contribute to inflammation
in the central nervous system (CNS). In experimental autoimmune encephalomyelitis
(EAE), we found that inflammatory cytokine-producing Th17 cells showed increased
CD73 expression as disease progressed. We therefore hypothesized that CD73 could be
important for limiting the expansion or pathogenic function of Th17 cells in autoimmune
inflammation of the CNS. Surprisingly, EAE development was not enhanced or inhibited by
CD73 deficiency; there was correspondingly no difference in induction of Th17-associated
cytokines IL-17, IFNγ or GM-CSF or recruitment of either inflammatory or regulatory cells to
the central nervous system. We confirmed that CD73 was similarly not required for differentiation
of Th17 cells in vitro. These data show that while CD73 expression is regulated during
EAE, this enzyme is not absolutely required to either promote or limit Th17 cell expansion or
EAE severity
Date Issued
2017-03-13
Date Acceptance
2017-02-21
Citation
PLoS ONE, 2017, 12 (3)
ISSN
1932-6203
Publisher
Public Library of Science (PLoS)
Journal / Book Title
PLoS ONE
Volume
12
Issue
3
Copyright Statement
© 2017 Hernandez-Mir, McGeachy. This
is an open access article distributed under the
terms of the Creative Commons Attribution
License, which permits unrestricted use,
distribution, and reproduction in any medium,
provided the original author and source are
credited
is an open access article distributed under the
terms of the Creative Commons Attribution
License, which permits unrestricted use,
distribution, and reproduction in any medium,
provided the original author and source are
credited
License URL
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
REGULATORY T-CELLS
CENTRAL-NERVOUS-SYSTEM
CYTOKINE GM-CSF
TGF-BETA
CUTTING EDGE
T(H)17 CELLS
IN-VIVO
NEUROINFLAMMATION
ADENOSINE
CD39
Publication Status
Published
Article Number
e0173655