Expression of ectonucleotidase CD39 by Foxp3+ Treg cells: hydrolysis of extracellular ATP and immune suppression - PubMed (original) (raw)
. 2007 Aug 15;110(4):1225-32.
doi: 10.1182/blood-2006-12-064527. Epub 2007 Apr 20.
Markus Kleinewietfeld, Diletta Di Mitri, Alexander Sternjak, Adamo Diamantini, Raffaella Giometto, Sabine Höpner, Diego Centonze, Giorgio Bernardi, Maria Luisa Dell'Acqua, Paolo Maria Rossini, Luca Battistini, Olaf Rötzschke, Kirsten Falk
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- PMID: 17449799
- DOI: 10.1182/blood-2006-12-064527
Free article
Expression of ectonucleotidase CD39 by Foxp3+ Treg cells: hydrolysis of extracellular ATP and immune suppression
Giovanna Borsellino et al. Blood. 2007.
Free article
Abstract
In the immune system, extracellular ATP functions as a "natural adjuvant" that exhibits multiple proinflammatory effects. It is released by damaged cells as an indicator of trauma and cell death but can be inactivated by CD39 (nucleoside triphosphate diphosphohydrolase-1 [NTPDase 1]), an ectoenzyme that degrades ATP to AMP. Here, we show that CD39 is expressed primarily by immune-suppressive Foxp3(+) regulatory T (Treg) cells. In mice, the enzyme is present on virtually all CD4(+)CD25(+) cells. CD39 expression is driven by the Treg-specific transcription factor Foxp3 and its catalytic activity is strongly enhanced by T-cell receptor (TCR) ligation. Activated Treg cells are therefore able to abrogate ATP-related effects such as P2 receptor-mediated cell toxicity and ATP-driven maturation of dendritic cells. Also, human Treg cells express CD39. In contrast to mice, CD39 expression in man is restricted to a subset of Foxp3(+) regulatory effector/memory-like T (T(REM)) cells. Notably, patients with the remitting/relapsing form of multiple sclerosis (MS) have strikingly reduced numbers of CD39(+) Treg cells in the blood. Thus, in humans CD39 is a marker of a Treg subset likely involved in the control of the inflammatory autoimmune disease.
Comment in
- Hydrolysis of extracellular ATP and immune suppression: humans versus mice.
Gorini S, la Sala A. Gorini S, et al. Blood. 2008 Jan 15;111(2):964-5; author reply 965-6. doi: 10.1182/blood-2007-09-111203. Blood. 2008. PMID: 18182581 No abstract available.
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