Abstract
Purpose :
Our previous work demonstrates that memory T cells mediate the retinopathy in a murine model of chronic autoimmune uveitis (CAU), and IL-7 is a critical surviving factor for memory Th17 cells. Herein, we aim to investigate the effect of blocking IL-7 in modulating clinical disease and memory Th17 cells in CAU.
Methods :
CAU was induced in wild-type C57BL/6J mice by immunization with interphotoreceptor retinoid-binding protein (IRBP) peptides emulsified in complete Freund’s adjuvant (CFA), along with Bordetella pertussis toxin injection. The establishment of CAU was confirmed by digital fundus imaging at week 12. CAU mice then received intraperitoneal injections of 100μg anti-IL-7 antibody (Ab) or the control IgG every other day for 2 weeks for total of 8 injections. The clinical disease was assessed weekly by fundoscopy. After a 4-week follow-up, mice were euthanized, and ocular and lymphoid tissues were collected and analyzed for memory Th17 response by staining CD3, CD4, CD44, and IL-17 using flow cytometry.
Results :
At the end of the 2-week treatment, CAU mice receiving the anti-IL-7 Ab showed a significantly reduced score of retinal vessel cuffing (2.8±0.6) compared to pre-treatment (4.6±1.0, p = 0.04), and this effect persisted until week 4 (1.2±0.4, p = 0.006), accompanied with significantly reduced retinal tissue infiltrates observed on fundus imaging (score of 1.8±0.5 vs. pre-treatment of 3.3±0.3, p = 0.02). In contrast, those treated with the control IgG did not show any significant clinical changes during the 4-week period. The cumulative response rates at week 4 were 67% for the anti-IL-7 Ab group and 0 for the control group (hazard ratio: 7.60, 95% CI: 0.98 – 58.88, p = 0.05). Flow cytometric analysis demonstrated that the anti-IL-7 Ab treatment led to a nearly complete depletion of T cells infiltrated in the retinal tissues in CAU, as well as an effective reduction of memory Th17 cells in the eye-draining lymph nodes compared to the control treatment (0.35±0.09% vs. 0.95±0.09%, p = 0.05).
Conclusions :
Our data suggest that the depletion of memory Th17 cells by blocking IL-7 is a promising therapeutic strategy for chronic uveitis.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.