Generation of anti-inflammatory adenosine by leukocytes is regulated by TGF-β.
Levels of anti-inflammatory extracellular adenosine are controlled by the sequential action of the ectonucleotidases CD39 and CD73, whose expression in CD4(+) T cells has been associated with natural regulatory T cells (nTregs). We here show that CD73 expression on activated murine CD4(+) T cells is...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2011
|
| _version_ | 1826260079895117824 |
|---|---|
| author | Regateiro, F Howie, D Nolan, K Agorogiannis, E Greaves, D Cobbold, S Waldmann, H |
| author_facet | Regateiro, F Howie, D Nolan, K Agorogiannis, E Greaves, D Cobbold, S Waldmann, H |
| author_sort | Regateiro, F |
| collection | OXFORD |
| description | Levels of anti-inflammatory extracellular adenosine are controlled by the sequential action of the ectonucleotidases CD39 and CD73, whose expression in CD4(+) T cells has been associated with natural regulatory T cells (nTregs). We here show that CD73 expression on activated murine CD4(+) T cells is induced by TGF-β independently of Foxp3 expression, operates at the transcriptional level and translates into gain of functional capacity to generate adenosine. In the presence of AMP, CD73 induced by TGF-β generates adenosine able to suppress proliferation of activated CD4(+) T cells in vitro. These effects are contextual and opposed by proinflammatory cytokines. CD73 is also upregulated by TGF-β in CD8(+) T cells, DCs and macrophages, so providing an amplification mechanism for adenosine generation in tissue microenvironments. Together, these findings expose a novel anti-inflammatory role for TGF-β. |
| first_indexed | 2024-03-06T18:59:56Z |
| format | Journal article |
| id | oxford-uuid:13304800-5fb3-48d6-a10a-01cb09d3ef3a |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:59:56Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:13304800-5fb3-48d6-a10a-01cb09d3ef3a2022-03-26T10:12:19ZGeneration of anti-inflammatory adenosine by leukocytes is regulated by TGF-β.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:13304800-5fb3-48d6-a10a-01cb09d3ef3aEnglishSymplectic Elements at Oxford2011Regateiro, FHowie, DNolan, KAgorogiannis, EGreaves, DCobbold, SWaldmann, HLevels of anti-inflammatory extracellular adenosine are controlled by the sequential action of the ectonucleotidases CD39 and CD73, whose expression in CD4(+) T cells has been associated with natural regulatory T cells (nTregs). We here show that CD73 expression on activated murine CD4(+) T cells is induced by TGF-β independently of Foxp3 expression, operates at the transcriptional level and translates into gain of functional capacity to generate adenosine. In the presence of AMP, CD73 induced by TGF-β generates adenosine able to suppress proliferation of activated CD4(+) T cells in vitro. These effects are contextual and opposed by proinflammatory cytokines. CD73 is also upregulated by TGF-β in CD8(+) T cells, DCs and macrophages, so providing an amplification mechanism for adenosine generation in tissue microenvironments. Together, these findings expose a novel anti-inflammatory role for TGF-β. |
| spellingShingle | Regateiro, F Howie, D Nolan, K Agorogiannis, E Greaves, D Cobbold, S Waldmann, H Generation of anti-inflammatory adenosine by leukocytes is regulated by TGF-β. |
| title | Generation of anti-inflammatory adenosine by leukocytes is regulated by TGF-β. |
| title_full | Generation of anti-inflammatory adenosine by leukocytes is regulated by TGF-β. |
| title_fullStr | Generation of anti-inflammatory adenosine by leukocytes is regulated by TGF-β. |
| title_full_unstemmed | Generation of anti-inflammatory adenosine by leukocytes is regulated by TGF-β. |
| title_short | Generation of anti-inflammatory adenosine by leukocytes is regulated by TGF-β. |
| title_sort | generation of anti inflammatory adenosine by leukocytes is regulated by tgf β |
| work_keys_str_mv | AT regateirof generationofantiinflammatoryadenosinebyleukocytesisregulatedbytgfb AT howied generationofantiinflammatoryadenosinebyleukocytesisregulatedbytgfb AT nolank generationofantiinflammatoryadenosinebyleukocytesisregulatedbytgfb AT agorogiannise generationofantiinflammatoryadenosinebyleukocytesisregulatedbytgfb AT greavesd generationofantiinflammatoryadenosinebyleukocytesisregulatedbytgfb AT cobbolds generationofantiinflammatoryadenosinebyleukocytesisregulatedbytgfb AT waldmannh generationofantiinflammatoryadenosinebyleukocytesisregulatedbytgfb |