Choroidal γδ T cells in protection against retinal pigment epithelium and retinal injury

Zhenyang Zhao, Yuejin Liang, Yin Liu, Pei Xu, Miles J. Flamme-Wiese, Deming Sun, Jiaren Sun, Robert F. Mullins, Yan Chen, Jiyang Cai

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

γδ T cells located near the epithelial barrier are integral components of local inflammatory and innate immune responses. We have previously reported the presence of choroidal γδ T cells in a model of chronic degeneration of the retinal pigment epithelium (RPE). The goals of the current study were to further define the functions of choroidal γδ T cells and to explore the underlying mechanisms of their action. Our data demonstrate that choroidal γδ T cells are activated by RPE injury in response to NaIO3 treatment, and that they express genes that encode immunosuppressive cytokines, such as IL-4 and IL-10. γδ–T-cell–deficient mice developed profound RPE and retinal damage at doses that caused minimal effects in wild-type mice, and adoptive transfer of γδ T cells prevented sensitization. Intravitreal injection of IL-4 and IL-10 ameliorated RPE toxicity that was induced by NaIO3. Ex vivo coculture of γδ T cells with RPE explants activated the production of anti-inflammatory cytokines via an aryl hydrocarbon receptor (AhR)–dependent mechanism. AhR deficiency abolished the protective effects of γδ T cells after adoptive transfer. Collectively, these findings define important roles for choroid γδ T cells in maintaining tissue homeostasis in the outer retina.—Zhao, Z., Liang, Y., Liu, Y., Xu, P., Flamme-Wiese, M. J., Sun, D., Sun, J., Mullins, R. F., Chen, Y., Cai, J. Choroidal γδ T cells in protection against retinal pigment epithelium and retinal injury.

Original languageEnglish (US)
Pages (from-to)4903-4916
Number of pages14
JournalFASEB Journal
Volume31
Issue number11
DOIs
StatePublished - Jan 1 2017

Keywords

  • AhR
  • Choriocapillaris drop out
  • Immune modulation
  • Inflammation

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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    Zhao, Z., Liang, Y., Liu, Y., Xu, P., Flamme-Wiese, M. J., Sun, D., Sun, J., Mullins, R. F., Chen, Y., & Cai, J. (2017). Choroidal γδ T cells in protection against retinal pigment epithelium and retinal injury. FASEB Journal, 31(11), 4903-4916. https://doi.org/10.1096/fj.201700533R