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...

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المؤلفون الرئيسيون: Regateiro, F, Howie, D, Nolan, K, Agorogiannis, E, Greaves, D, Cobbold, S, Waldmann, H
التنسيق: Journal article
اللغة:English
منشور في: 2011
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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.
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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
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