Islet-Derived eATP Fuels Autoreactive CD8+ T Cells and Facilitates the Onset of Type 1 Diabetes

• Published in: Diabetes (New York, N.Y.) Vol. 67; no. 10; pp. 2038 - 2053
• Main Authors: Tezza, Sara, Ben Nasr, Moufida, D’Addio, Francesca, Vergani, Andrea, Usuelli, Vera, Falzoni, Simonetta, Bassi, Roberto, Dellepiane, Sergio, Fotino, Carmen, Rossi, Chiara, Maestroni, Anna, Solini, Anna, Corradi, Domenico, Giani, Elisa, Mameli, Chiara, Bertuzzi, Federico, Pezzolesi, Marcus G., Wasserfall, Clive H., Atkinson, Mark A., Füchtbauer, Ernst-Martin, Ricordi, Camillo, Folli, Franco, Di Virgilio, Francesco, Pileggi, Antonello, Dhe-Paganon, Sirano, Zuccotti, Gian Vincenzo, Fiorina, Paolo
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01.10.2018
• Subjects: Adenosine Triphosphate - analogs & derivatives; Adenosine Triphosphate - metabolism; Adenosine Triphosphate - pharmacology; Animals; Autoimmunity - genetics; Autoimmunity - physiology; CD8-Positive T-Lymphocytes - metabolism; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - metabolism; Female; Flow Cytometry; Humans; Immunology and Transplantation; Lymphocyte Activation - drug effects; Mice; Mice, Inbred BALB C; Mice, Inbred NOD; Mutation - genetics; Receptors, Purinergic P2X7 - genetics; Receptors, Purinergic P2X7 - metabolism

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...