The STING-IFN-β-Dependent Axis Is Markedly Low in Patients with Relapsing-Remitting Multiple Sclerosis

Masanneck L, Eichler S, Vogelsang A, Korsen M, Wiendl H, Budde T, Meuth SG

Research article (journal) | Peer reviewed

Abstract

yclic GMP-AMP-synthase is a sensor of endogenous nucleic acids, which subsequently elicits a stimulator of interferon genes (STING)-dependent type I interferon (IFN) response defending us against viruses and other intracellular pathogens. This pathway can drive pathological inflammation, as documented for type I interferonopathies. In contrast, specific STING activation and subsequent IFN-β release have shown beneficial effects on experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS). Although less severe cases of relapse-remitting MS (RRMS) are treated with IFN-β, there is little information correlating aberrant type I IFN signaling and the pathologic conditions of MS. We hypothesized that there is a link between STING activation and the endogenous production of IFN-β during neuroinflammation. Gene expression analysis in EAE mice showed thatStinglevel decreased in the peripheral lymphoid tissue, while its level increased within the central nervous system over the course of the disease. Similar patterns could be verified in peripheral immune cells during the acute phases of RRMS in comparison to remitting phases and appropriately matched healthy controls. Our study is the first to provide evidence that the STING/IFN-β-axis is downregulated in RRMS patients, meriting further intensified research to understand its role in the pathophysiology of MS and potential translational applications.

Details about the publication

JournalInternational Journal of Molecular Sciences ( Int J Mol Sci)
Volume21(23):9249
StatusPublished
Release year2020 (04/12/2020)
Language in which the publication is writtenEnglish
DOI10.3390/ijms21239249
KeywordsSTING; cGAMP; interferon-beta; multiple sclerosis; RRMS; EAE

Authors from the University of Münster

Budde, Thomas
Institute of Physiology I (Neurophysiology)
Eichler, Susann
Department of Neurology [closed]
Meuth, Sven
Department for Neurology
Vogelsang, Anna
Department for Neurology
Wiendl, Heinz Siegfried
Department for Neurology