CD73-mediated adenosine production promotes stem cell-like properties in mouse Tc17 cells

Immunology
Felipe Flores-SantibáñezDaniela Sauma

Abstract

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-β (TGF-β), and hence CD73 expression is related to the acquisition of immunosuppressive potential by these cells. TGF-β 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-γ 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...Continue Reading

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Citations

Mar 5, 2017·Immunological Reviews·Bertrand AllardJohn Stagg
Feb 24, 2018·Frontiers in Immunology·Felipe Flores-SantibáñezDaniela Sauma
Jan 30, 2019·International Journal of Molecular Sciences·Marta VuerichMaria Serena Longhi
Mar 13, 2020·Journal of Translational Medicine·Mariaelena CaponePaolo A Ascierto
Apr 30, 2020·Signal Transduction and Targeted Therapy·Chao NiJian Huang
Apr 27, 2019·Frontiers in Immunology·Simone de LeveVerena Jendrossek
Apr 14, 2020·Cancer Cell International·Li-Li FengXin Wang
Jun 22, 2019·Immunotherapy·Siqi ChenBin Zhang
Jan 19, 2021·Biochemical Pharmacology·Maria Serena LonghiSimon C Robson
Mar 9, 2021·Frontiers in Cell and Developmental Biology·Pedro BriceñoDaniela Sauma
May 15, 2018·Immunology Letters·David AllardJohn Stagg
Jul 16, 2021·Life Sciences·Elham BaghbaniBehzad Baradaran

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