Progression of type 1 diabetes from the prediabetic stage is controlled by interferon-α signaling.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 28325871.
- Also identified by DOI 10.1073/pnas.1700878114 and PMC identifier 5389329.
- No licence information is recorded for this record.
- Because redistribution is not established, this page shows the abstract only. Follow the links below for the full text.
Abstract
Blockade of IFN-α but not IFN-β signaling using either an antibody or a selective S1PR1 agonist, CYM-5442, prevented type 1 diabetes (T1D) in the mouse <i>Rip</i>-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 β cells. Second, CYM-5442 induced an exhaustion signature in antiself T cells by up-regulating the negative immune regulator receptor genes <i>Pdcd1, Lag3, Ctla4, Tigit</i>, and <i>Btla</i>, thereby limiting their killing ability. By such means, insulin production was preserved and glucose regulation maintained, and a mechanism for S1PR1 immunomodulation described.
Medical subject headings
- Diabetes Mellitus, Type 1
- Indans
- Interferon-alpha
- Oxadiazoles
- Prediabetic State
- Receptors, Lysosphingolipid
- T-Lymphocytes