Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 41, Issue 10, Pages 2955-2965Publisher
WILEY
DOI: 10.1002/eji.201141512
Keywords
Adenosine; CD73; Immune regulation; Lymphocytes; TGF-beta
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Funding
- UK Medical Research Council [G7904009, G1000215]
- Fundacaopara a Ciencia e Tecnologia, Portugal
- Medical Research Council [G7904009, G1000215] Funding Source: researchfish
- MRC [G7904009, G1000215] Funding Source: UKRI
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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-beta 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-beta 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-beta 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-beta.
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