@article{1de9585cf76c417ab664b0d025074cb6,
title = "Type I Interferon Therapy Limits CNS Autoimmunity by Inhibiting CXCR3-Mediated Trafficking of Pathogenic Effector T Cells",
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.",
keywords = "type I interferon, CXCR3, experimental autoimmune uveitis, human uveitis",
author = "Weiwei Wang and Chong, {Wai Po} and Chunmei Li and Zilin Chen and Sihan Wu and Hongyan Zhou and Ying Wan and Wanjun Chen and Igal Gery and Yizhi Liu and Caspi, {Rachel R.} and Jun Chen",
note = "Funding information: We thank Dr. Howard Young (NCI) for critical review and editing of the manuscript, Dr. Joshua Farber (NIAID) for helpful discussion, Dr. Eric F Wawrousek (NEI) for generating the HEL Tg mice, and the staff of the Zhongshan Ophthalmic Center Flow Cytometry Core and the NEI Flow Cytometry and Biological Imaging Cores for excellent technical support. This study was funded by the Intramural Research Program of the National Eye Institute, NIH (project numbers EY000069 and EY000184); the Natural Science Foundation of Guangdong Province (grant numbers 2014A030313048 and 2017A030313836); the Guangzhou Science and Technology Program key projects (grant number 201604020082); and the Fundamental Research Fund for the State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center. Publisher copyright: {\textcopyright} 2019 The Author(s).",
year = "2019",
month = jul,
day = "9",
doi = "10.1016/j.celrep.2019.06.021",
language = "English",
volume = "28",
pages = "486--497.e4",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "2",
}
