| First Author | Flores-Santibáñez F | Year | 2015 |
| Journal | Immunology | Volume | 146 |
| Issue | 4 | Pages | 582-94 |
| PubMed ID | 26331349 | Mgi Jnum | J:246646 |
| Mgi Id | MGI:5922735 | Doi | 10.1111/imm.12529 |
| Citation | Flores-Santibanez F, et al. (2015) CD73-mediated adenosine production promotes stem cell-like properties in mouse Tc17 cells. Immunology 146(4):582-94 |
| abstractText | 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-beta (TGF-beta), and hence CD73 expression is related to the acquisition of immunosuppressive potential by these cells. TGF-beta 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-gamma 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. |
