Chen, Y-H; Eskandarpour, M; Gondrand, A; Zhang, X; Gu, R; Galatowicz, G; Lightman, SL; Chen, Y-H; Eskandarpour, M; Gondrand, A; Zhang, X; Gu, R; Galatowicz, G; Lightman, SL; Calder, VL; - view fewer (2020) Functionally distinct IFN-γ⁺ IL-17A⁺ Th cells in experimental autoimmune uveitis: T-cell heterogeneity, migration, and steroid response. European Journal of Immunology 10.1002/eji.202048616. (In press).

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Abstract

Immunopathogenic roles for both Th1 (CD4^{+} IFN-γ^{+}) and Th17 (CD4^{+} IL-17A^{+}) cells have been demonstrated in experimental autoimmune uveitis (EAU). However, the role for Th17/Th1 (CD4^{+} T cells co-expressing IFN-γ and IL-17A) cells in EAU is not yet understood. Using interphotoreceptor retinoid-binding protein peptide-induced EAU in mice, we found increased levels of Th17/Th1 cells in EAU retinae (mean 9.6 ± 4.2%) and draining LNs (mean 8.4 ± 3.9%; p = 0.01) relative to controls. Topical dexamethasone treatment effectively reduced EAU severity and decreased retinal Th1 cells (p = 0.01), but had no impact on retinal Th17/Th1 or Th17 cells compared to saline controls. Using in vitro migration assays with mouse CNS endothelium, we demonstrated that Th17/Th1 cells were significantly increased within the migrated population relative to controls (mean 15.6 ± 9.5% vs. 1.9 ± 1.5%; p = 0.01). Chemokine receptor profiles of Th17/Th1 cells (CXCR3 and CCR6) did not change throughout the transendothelial migration process and were unaffected by dexamethasone treatment. These findings support a role for Th17/Th1 cells in EAU and their resistance to steroid inhibition suggests the importance of targeting both Th17 and Th17/Th1 cells for improving therapy.

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