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

作者：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 · 发表于：Cell Reports · 年份：2019 · DOI：10.1016/j.celrep.2019.06.021 · 被引用次数：31 · 研究领域：Systemic Lupus Erythematosus Research、Ocular Diseases and Behçet’s Syndrome、interferon and immune responses

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.