| First Author | Tezza S | Year | 2018 |
| Journal | Diabetes | Volume | 67 |
| Issue | 10 | Pages | 2038-2053 |
| PubMed ID | 30065030 | Mgi Jnum | J:265165 |
| Mgi Id | MGI:6199334 | Doi | 10.2337/db17-1227 |
| Citation | Tezza S, et al. (2018) Islet-Derived eATP Fuels Autoreactive CD8(+) T Cells and Facilitates the Onset of Type 1 Diabetes. Diabetes 67(10):2038-2053 |
| abstractText | Extracellular ATP (eATP) activates T cells by engaging the P2X7R receptor. We identified two loss-of-function P2X7R mutations that are protective against type 1 diabetes (T1D) and thus hypothesized that eATP/P2X7R signaling may represent an early step in T1D onset. Specifically, we observed that in patients with newly diagnosed T1D, P2X7R is upregulated on CD8(+) effector T cells in comparison with healthy control subjects. eATP is released at high levels by human/murine islets in vitro in high-glucose/inflammatory conditions, thus upregulating P2X7R on CD8(+) T cells in vitro. P2X7R blockade with oxidized ATP reduces the CD8(+) T cell-mediated autoimmune response in vitro and delays diabetes onset in NOD mice. Autoreactive CD8(+) T-cell activation is highly dependent upon eATP/P2X7R-mediated priming, while a novel sP2X7R recombinant protein abrogates changes in metabolism and the autoimmune response associated with CD8(+) T cells. eATP/P2X7R signaling facilitates the onset of autoimmune T1D by fueling autoreactive CD8(+) cells and therefore represents a novel targeted therapeutic for the disorder. |
