Type I Interferon Therapy Limits CNS Autoimmunity by Inhibiting CXCR3-Mediated Trafficking of Pathogenic Effector T Cells

Weiwei Wang, Wai Po Chong, Chunmei Li, Zilin Chen, Sihan Wu, Hongyan Zhou, Ying Wan, Wanjun Chen, Igal Gery, Yizhi Liu, Rachel R. Caspi*, Jun Chen*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

16 Citations (Scopus)

Abstract

Type I interferons (IFNs) have therapeutic potential in CNS autoimmune diseases, such as uveitis, but the molecular mechanisms remain unclear. Using a T cell-transfer model of experimental autoimmune uveitis (EAU), we found that IFN-α/β treatment inhibited the migration of IFN-γ-producing pathogenic CD4+ T cells to effector sites. IFN-α/β upregulated the expression of the cognate ligands CXCL9, CXCL10, and CXCL11, causing ligand-mediated downregulation of CXCR3 expression and effector T cell retention in the spleen. Accordingly, type I IFN did not alter EAU progression in CXCR3−/− mice. In uveitis patients, disease exacerbations correlated with reduced serum IFN-α concentrations. IFN-α/β reduced CXCR3 expression and migration by human effector T cells, and these parameters were associated with the therapeutic efficacy of IFN-α in uveitis patients. Our findings provide insight into the molecular basis of type I IFN therapy for CNS autoimmune diseases and identify CXCR3 as a biomarker for effective type I IFN immunotherapy.

Original languageEnglish
Pages (from-to)486-497.e4
Number of pages16
JournalCell Reports
Volume28
Issue number2
DOIs
Publication statusPublished - 9 Jul 2019

User-Defined Keywords

  • type I interferon
  • CXCR3
  • experimental autoimmune uveitis
  • human uveitis

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