| First Author | Cekic C | Year | 2013 |
| Journal | J Exp Med | Volume | 210 |
| Issue | 12 | Pages | 2693-706 |
| PubMed ID | 24145516 | Mgi Jnum | J:207727 |
| Mgi Id | MGI:5559424 | Doi | 10.1084/jem.20130249 |
| Citation | Cekic C, et al. (2013) Extracellular adenosine regulates naive T cell development and peripheral maintenance. J Exp Med 210(12):2693-706 |
| abstractText | Adenosine produced as a byproduct of metabolic activity is present in all tissues and produces dose-dependent suppression of TCR signaling. Naive T cell maintenance depends on inhibition of TCR signals by environmental sensors, which are yet to be fully defined. We produced mice with a floxed adenosine A2A receptor (A2AR) gene, Adora2a, and show that either global A2AR deletion or cre-mediated T cell deletion elicits a decline in the number of naive but not memory T cells. A2AR signaling maintains naive T cells in a quiescent state by inhibiting TCR-induced activation of the phosphatidylinositide 3-kinase (PI3K)-AKT pathway, thereby reducing IL-7Ralpha down-regulation and naive T cell apoptosis. Patterns of IL-7Ralpha expression on T cells in chimeric mice reconstituted with Adora2a(+/+) and Adora2a(-/-) bone marrow cells suggest that decreased IL-7Ralpha in naive T cells is a cell-intrinsic consequence of Adora2a deletion. In addition, A2AR expression increases in early thymic T cell development and contributes to progression of double-negative thymic precursors to single-positive thymocytes with increased IL-7Ralpha expression. Therefore, A2AR signaling regulates T cell development and maintenance to sustain normal numbers of naive T cells in the periphery. |
