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

Felipe Flores-Santibáñez, Dominique Fernández, Daniel Meza, Gabriela Tejón, Leonardo Vargas, Lorena Varela-Nallar, Sebastián Arredondo, Victoria Guixé, Mario Rosemblatt, María Rosa Bono, Daniela Sauma

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva

23 Citas (Scopus)

Resumen

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 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.

Idioma originalInglés
Páginas (desde-hasta)582-594
Número de páginas13
PublicaciónImmunology
Volumen146
N.º4
DOI
EstadoPublicada - 1 dic. 2015

Áreas temáticas de ASJC Scopus

  • Inmulogía y alergología
  • Inmunología

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