| First Author | Marro BS | Year | 2017 |
| Journal | Proc Natl Acad Sci U S A | Volume | 114 |
| Issue | 14 | Pages | 3708-3713 |
| PubMed ID | 28325871 | Mgi Jnum | J:242031 |
| Mgi Id | MGI:5904221 | Doi | 10.1073/pnas.1700878114 |
| Citation | Marro BS, et al. (2017) Progression of type 1 diabetes from the prediabetic stage is controlled by interferon-alpha signaling. Proc Natl Acad Sci U S A 114(14):3708-3713 |
| abstractText | Blockade of IFN-alpha but not IFN-beta signaling using either an antibody or a selective S1PR1 agonist, CYM-5442, prevented type 1 diabetes (T1D) in the mouse Rip-LCMV T1D model. First, treatment with antibody or CYM-5442 limited the migration of autoimmune "antiself" T cells to the external boundaries around the islets and prevented their entry into the islets so they could not be positioned to engage, kill, and thus remove insulin-producing beta cells. Second, CYM-5442 induced an exhaustion signature in antiself T cells by up-regulating the negative immune regulator receptor genes Pdcd1, Lag3, Ctla4, Tigit, and Btla, thereby limiting their killing ability. By such means, insulin production was preserved and glucose regulation maintained, and a mechanism for S1PR1 immunomodulation described. |
