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Expression of ectonucleotidase CD39 by Foxp3+ Treg cells: hydrolysis of extracellular ATP and immune suppression

Item Type:Article
Title:Expression of ectonucleotidase CD39 by Foxp3+ Treg cells: hydrolysis of extracellular ATP and immune suppression
Creators Name:Borsellino, G. and Kleinewietfeld, M. and Di Mitri, D. and Sternjak, A. and Diamantini, A. and Giometto, R. and Hoepner, S. and Centonze, D. and Bernardi, G. and Dell'Acqua, M.L. and Rossini, P.M. and Battistini, L. and Roetzschke, O. and Falk, K.
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 cells (Treg). 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 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 cells (TREM). Notably, patients suffering of 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.
Keywords:Adenosine Triphosphate, CD Antigens, Apyrase, Dendritic Cells, Forkhead Transcription Factors, Hydrolysis, Immunosuppression, Relapsing-Remitting Multiple Sclerosis, Regulatory T-Lymphocytes, Animals, Mice
Source:Blood
ISSN:0006-4971
Publisher:American Society of Hematology (U.S.A.)
Volume:110
Number:4
Page Range:1225-1232
Date:15 August 2007
Official Publication:https://doi.org/10.1182/blood-2006-12-064527
PubMed:View item in PubMed

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