Pluto Bioinformatics

GSE96541: Blockade of IFN-alpha by antibody or CYM-5442 reveals a unique transcriptional gene signature in autoimmune CD8+ T cells and pancreatic islets

Bulk RNA sequencing

Blockade of interferon (IFN)-alpha but not IFN-beta signaling using either an antibody or a selective S1PR1 agonist, CYM-5442, prevented 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 cells. Second, CYM-5442 induced an exhaustion signature in antiself T cells by upregulating 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 novel mechanism for S1PR1 immunomodulation described. SOURCE: Michael,B. A.,Oldstone (mbaobo@scripps.edu) - The Scripps Research Institute