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

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          Summary

          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 ( TGFβ), and hence CD73 expression is related to the acquisition of immunosuppressive potential by these cells. TGFβ 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.

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          Author and article information

          Journal
          Immunology
          Immunology
          10.1111/(ISSN)1365-2567
          IMM
          Immunology
          John Wiley and Sons Inc. (Hoboken )
          0019-2805
          1365-2567
          29 September 2015
          December 2015
          : 146
          : 4 ( doiID: 10.1111/imm.2015.146.issue-4 )
          : 582-594
          Affiliations
          [ 1 ] Departamento de Biologia Facultad de Ciencias Universidad de Chile Santiago Chile
          [ 2 ] Centro de Investigaciones Biomedicas Facultad de Ciencias Biológicas y Facultad de Medicina Universidad Andres Bello Santiago Chile
          [ 3 ] Facultad de Ciencias Biologicas Universidad Andres Bello Santiago Chile
          [ 4 ] Fundacion Ciencia & Vida Santiago Chile
          Author notes
          [*] [* ] Correspondence: Dr Daniela Sauma, Departamento de Biologia, Facultad de Ciencias, Universidad de Chile, Las Palmeras 3425, Ñuñoa, Santiago, Chile. Email: dsauma@ 123456u.uchile.cl

          Senior author: Daniela Sauma

          Article
          PMC4693903 PMC4693903 4693903 IMM12529
          10.1111/imm.12529
          4693903
          26331349
          768fa880-b3c1-4449-a955-ade0c614e1e3
          © 2015 John Wiley & Sons Ltd
          History
          : 20 May 2015
          : 08 August 2015
          : 25 August 2015
          Page count
          Pages: 13
          Funding
          Funded by: FONDECYT
          Award ID: 11121478
          Award ID: 1140431
          Award ID: PFB‐16
          Categories
          Original Article
          Original Articles
          Custom metadata
          2.0
          imm12529
          December 2015
          Converter:WILEY_ML3GV2_TO_NLMPMC version:4.7.2 mode:remove_FC converted:22.12.2015

          tumour immunology,adenosine, CD73,cell differentiation,stem cell,Tc17

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