Foxp3(+) Tregs are recruited to the retina to repair pathological angiogenesis
AuthorDeliyanti, D; Talia, DM; Zhu, T; Maxwell, MJ; Agrotis, A; Jerome, JR; Hargreaves, EM; Gerondakis, S; Hibbs, ML; Mackay, F; ...
Source TitleNature Communications
PublisherNATURE PUBLISHING GROUP
AffiliationSchool of Biomedical Sciences
Microbiology and Immunology
Anatomy and Neuroscience
Document TypeJournal Article
CitationsDeliyanti, D., Talia, D. M., Zhu, T., Maxwell, M. J., Agrotis, A., Jerome, J. R., Hargreaves, E. M., Gerondakis, S., Hibbs, M. L., Mackay, F. & Wilkinson-Berka, J. L. (2017). Foxp3(+) Tregs are recruited to the retina to repair pathological angiogenesis. NATURE COMMUNICATIONS, 8 (1), https://doi.org/10.1038/s41467-017-00751-w.
Access StatusOpen Access
Neovascular retinopathies are major causes of vision loss; yet treatments to prevent the condition are inadequate. The role of regulatory T cells in neovascular retinopathy is unknown. Here we show that in retinopathy regulatory T cells are transiently increased in lymphoid organs and the retina, but decline when neovascularization is established. The decline is prevented following regulatory T cells expansion with an IL-2/anti-IL-2 mAb complex or the adoptive transfer of regulatory T cells. Further, both approaches reduce vasculopathy (vaso-obliteration, neovascularization, vascular leakage) and alter the activation of Tmem119+ retinal microglia. Our in vitro studies complement these findings, showing that retinal microglia co-cultured with regulatory T cells exhibit a reduction in co-stimulatory molecules and pro-inflammatory mediators that is attenuated by CTLA-4 blockade. Collectively, we demonstrate that regulatory T cells are recruited to the retina and, when expanded in number, repair the vasculature. Manipulation of regulatory T cell numbers is a previously unrecognized, and promising avenue for therapies to prevent blinding neovascular retinopathies.The local immune responses in the eye are attenuated to preserve sight. Surprisingly, Deliyanti et al. show that regulatory T cells (Tregs) take an active role in protecting the eye from neovascularization in oxygen-induced retinopathy, and that interventions that augment the retinal Treg numbers reduce neovascular retinopathy in mice.
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