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Progression of Type 1 Diabetes From the Prediabetic Stage Is Controlled by interferon-α Signaling

Progression of Type 1 Diabetes From the Prediabetic Stage Is Controlled by interferon-α Signaling

Brett S Marro, Brian C Ware, Jaroslav Zak, Juan Carlos de la Torre, Hugh Rosen, Michael B A Oldstone

Proc Natl Acad Sci U S A. 2017 Apr 4;114(14):3708-3713.

PMID: 28325871

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 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 β 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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1094042019	CYM-5442		1094042-01-9	Price

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