Interferon-β and FTY720 ameliorate progressive CNS inflammation via SOCS1-associated astrocyte signaling

Tsaktanis T, Beyer T, Nirschl L, Rotaru AI, Engleitner T, Öllinger R, Zuber F, Peter A, Zißler J, Tschurl V, Linnerbauer M, Lößlein L, Vandrey O, Rad R, Korn T, Rothhammer V (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Scientific Reports Nature Publishing Group: Open Access Journals - Option B

Book Volume: 16

Article Number: 9851

DOI: 10.1038/s41598-026-45303-9

Abstract

Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS) characterized by initially relapsing-remitting neurological deficits followed by progressive and largely irreversible disability driven by glial and neuronal pathology behind an increasingly restrictive blood–brain barrier, limiting access of peripherally applied therapeutics. Here, we show that combining sphingosine-1-phosphate receptor (S1PR) modulation with CNS-penetrant intranasal interferon-β (nIFN-β) enhances therapeutic effects relative to FTY720 alone in a chronic progressive EAE model. Combined treatment reduces CNS-infiltrating immune cells, decreases pro-inflammatory cytokine production, and augments protective glial programs in vivo, as well as in human astrocyte and microglial cell lines. Transcriptomic and perturbation analyses implicate SOCS1-associated signaling as a modulatory component of treatment-induced glial responses. Together, these findings support further investigation of combinatorial FTY720/nIFN-β strategies targeting CNS-intrinsic inflammatory pathways in progressive MS.

Authors with CRIS profile

Thanos Tsaktanis Department of Neurology Anne Peter Department of Neurology Julia Zißler Department of Neurology Vivienne Tschurl Department of Neurology Mathias Linnerbauer Department of Neurology Lena Lößlein Department of Neurology Oliver Vandrey Department of Neurology Veit Rothhammer Department of Neurology

Involved external institutions

Klinikum rechts der Isar DE Germany (DE)

How to cite

APA:

Tsaktanis, T., Beyer, T., Nirschl, L., Rotaru, A.I., Engleitner, T., Öllinger, R.,... Rothhammer, V. (2026). Interferon-β and FTY720 ameliorate progressive CNS inflammation via SOCS1-associated astrocyte signaling. Scientific Reports, 16. https://doi.org/10.1038/s41598-026-45303-9

MLA:

Tsaktanis, Thanos, et al. "Interferon-β and FTY720 ameliorate progressive CNS inflammation via SOCS1-associated astrocyte signaling." Scientific Reports 16 (2026).

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