Chen, Y-H;
Eskandarpour, M;
Gondrand, A;
Zhang, X;
Gu, R;
Galatowicz, G;
Lightman, SL;
(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.
| Type: | Article |
|---|---|
| Title: | Functionally distinct IFN-γ⁺ IL-17A⁺ Th cells in experimental autoimmune uveitis: T-cell heterogeneity, migration, and steroid response |
| Location: | Germany |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/eji.202048616 |
| Publisher version: | https://publons.com/publon/10.1002/eji.202048616 |
| Language: | English |
| Additional information: | © 2020 The Authors. European Journal of Immunology published by Wiley‐VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| Keywords: | IL-17A^{+}IFN-γ^{+}, T cell migration, Th17/Th1 cells, experimental autoimmune uveitis, steroid resistance |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10109611 |
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