Scholarlink

<p>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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月25日

查看全文
  • Thanos Tsaktanis,
  • Tobias Beyer,
  • Lucy Nirschl,
  • Alexandru-Ioan Rotaru,
  • Thomas Engleitner,
  • Rupert Öllinger,
  • Finnja Zuber,
  • Anne Peter,
  • Julia Zissler,
  • Vivienne Tschurl,
  • Mathias Linnerbauer,
  • Lena Lößlein,
  • Oliver Vandrey,
  • Roland Rad,
  • Thomas Korn,
  • Veit Rothhammer

摘要

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.