Generation of anti-inflammatory adenosine by leukocytes is regulated by TGF-β.

Journal article

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.

Authors: Regateiro, F; Howie, D; Nolan, K; Agorogiannis, E; Greaves, D

• Journal: Eur J Immunol
• Volume: 41
• Issue: 10
• Pages: 2955-2965
• Place of publication: Germany
• Publication date: 2011-10-01
• DOI: 10.1002/eji.201141512
• EISSN: 1521-4141
• ISSN: 0014-2980
• Language: English
• Keywords: CD4-Positive T-Lymphocytes; Lymphocyte Activation; Adenosine; 5'-Nucleotidase; Apyrase; Antigens, CD; T-Lymphocytes, Regulatory; Forkhead Transcription Factors; Dendritic Cells; Inflammation Mediators; Animals; Mice, Transgenic; Adenosine Monophosphate; CD8-Positive T-Lymphocytes; Macrophages; Antigens, Surface; Transforming Growth Factor beta; Mice, Inbred C57BL; Cell Proliferation; Leukocytes; Cytokines; Mice