| First Author | Wang W | Year | 2019 |
| Journal | Cell Rep | Volume | 28 |
| Issue | 2 | Pages | 486-497.e4 |
| PubMed ID | 31291583 | Mgi Jnum | J:284076 |
| Mgi Id | MGI:6380775 | Doi | 10.1016/j.celrep.2019.06.021 |
| Citation | Wang W, et al. (2019) Type I Interferon Therapy Limits CNS Autoimmunity by Inhibiting CXCR3-Mediated Trafficking of Pathogenic Effector T Cells. Cell Rep 28(2):486-497.e4 |
| abstractText | 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-alpha/beta treatment inhibited the migration of IFN-gamma-producing pathogenic CD4(+) T cells to effector sites. IFN-alpha/beta 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-alpha concentrations. IFN-alpha/beta reduced CXCR3 expression and migration by human effector T cells, and these parameters were associated with the therapeutic efficacy of IFN-alpha 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. |
