| First Author | Borsellino G | Year | 2007 |
| Journal | Blood | Volume | 110 |
| Issue | 4 | Pages | 1225-32 |
| PubMed ID | 17449799 | Mgi Jnum | J:145395 |
| Mgi Id | MGI:3834514 | Doi | 10.1182/blood-2006-12-064527 |
| Citation | Borsellino G, et al. (2007) Expression of ectonucleotidase CD39 by Foxp3+ Treg cells: hydrolysis of extracellular ATP and immune suppression. Blood 110(4):1225-32 |
| abstractText | 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. |
