CD73-mediated adenosine production promotes stem cell-like properties in mouse Tc17 cells
Author
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Flores Santibáñez, Felipe
Author
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Fernández, Dominique
Author
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Meza, Daniel
Author
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Tejón, Gabriela
Author
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Vargas, Leonardo
Author
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Varela Nallar, Lorena
Author
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Arredondo, Sebastián
Author
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Guixé Leguía, Victoria Cristina
Author
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Rosemblatt Silber, Mario César
Author
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Bono Merino, María Rosa
Author
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Sauma Mahaluf, Daniela
Admission date
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2016-03-09T19:12:55Z
Available date
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2016-03-09T19:12:55Z
Publication date
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2015
Cita de ítem
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Immunology, 146, 582–594
en_US
Identifier
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DOI: 10.1111/imm.12529
Identifier
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https://repositorio.uchile.cl/handle/2250/137003
General note
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Artículo de publicación ISI
en_US
Abstract
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The CD73 ectonucleotidase catalyses the hydrolysis of AMP to adenosine,
an immunosuppressive molecule. Recent evidence has demonstrated that
this ectonucleotidase is up-regulated in T helper type 17 cells when generated
in the presence of transforming growth factor-b (TGF-b), and hence
CD73 expression is related to the acquisition of immunosuppressive
potential by these cells. TGF-b is also able to induce CD73 expression in
CD8+ T cells but the function of this ectonucleotidase in CD8+ T cells is
still unknown. Here, we show that Tc17 cells present high levels of the
CD73 ectonucleotidase and produce adenosine; however, they do not suppress
the proliferation of CD4+ T cells. Interestingly, we report that adenosine
signalling through A2A receptor favours interleukin-17 production
and the expression of stem cell-associated transcription factors such as
tcf-7 and lef-1 but restrains the acquisition of Tc1-related effector molecules
such as interferon-c and Granzyme B by Tc17 cells. Within
the tumour microenvironment, CD73 is highly expressed in
CD62L+ CD127+ CD8+ T cells (memory T cells) and is down-regulated in
GZMB+ KLRG1+ CD8+ T cells (terminally differentiated T cells), demonstrating
that CD73 is expressed in memory/naive cells and is down-regulated
during differentiation. These data reveal a novel function of CD73
ectonucleotidase in arresting CD8+ T-cell differentiation and support the
idea that CD73-driven adenosine production by Tc17 cells may promote
stem cell-like properties in Tc17 cells.