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

Tools

Item Type:	Article
Title:	Expression of ectonucleotidase CD39 by Foxp3+ Treg cells: hydrolysis of extracellular ATP and immune suppression
Creators Name:	Borsellino, G., Kleinewietfeld, M., Di Mitri, D., Sternjak, A., Diamantini, A., Giometto, R., Hoepner, S., Centonze, D., Bernardi, G., Dell'Acqua, M.L., Rossini, P.M., Battistini, L., 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
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

Repository Staff Only: item control page