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

doi:10.1096/fj.201700533R

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

Journal article

Open access

Peer reviewed

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 and Jiyang Cai

The FASEB journal, Vol.31(11), pp.4903-4916

11/2017

DOI: 10.1096/fj.201700533R

PMCID: PMC5636697

PMID: 28729290

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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 NaIO 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 NaIO coculture of γδ T cells with RPE explants activated the production of anti-inflammatory cytokines 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.

Basic Helix-Loop-Helix Transcription Factors - genetics

Retinal Pigment Epithelium - injuries

Receptors, Aryl Hydrocarbon - genetics

Corneal Dystrophies, Hereditary - genetics

Corneal Dystrophies, Hereditary - therapy

Receptors, Antigen, T-Cell, gamma-delta - genetics

Receptors, Antigen, T-Cell, gamma-delta - immunology

Iodates - toxicity

Adoptive Transfer

T-Lymphocytes - transplantation

Mice, Knockout

Corneal Dystrophies, Hereditary - immunology

Interleukin-4 - immunology

Animals

Interleukin-10 - genetics

Retinal Pigment Epithelium - immunology

Basic Helix-Loop-Helix Transcription Factors - immunology

T-Lymphocytes - immunology

Corneal Dystrophies, Hereditary - chemically induced

Mice

Interleukin-4 - genetics

T-Lymphocytes - pathology

Interleukin-10 - immunology

Receptors, Aryl Hydrocarbon - immunology

Details

Title: Subtitle: Choroidal γδ T cells in protection against retinal pigment epithelium and retinal injury
Creators: Zhenyang Zhao - Department of Ophthalmology and Visual Sciences, University of Texas Medical Branch, Galveston, Texas, USA
Yuejin Liang - Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA
Yin Liu - Department of Neurobiology and Anatomy, University of Texas Health Science Center at Houston, Houston, Texas, USA
Pei Xu - Department of Ophthalmology and Visual Sciences, University of Texas Medical Branch, Galveston, Texas, USA
Miles J Flamme-Wiese - Stephen A. Wynn Institute for Vision Research, University of Iowa, Iowa City, Iowa, USA
Deming Sun - Doheny Eye Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA
Jiaren Sun - The University of Texas Medical Branch at Galveston
Robert F Mullins - Stephen A. Wynn Institute for Vision Research, University of Iowa, Iowa City, Iowa, USA
Yan Chen - The University of Texas Medical Branch at Galveston
Jiyang Cai - Department of Ophthalmology and Visual Sciences, University of Texas Medical Branch, Galveston, Texas, USA; jicai@utmb.edu
Resource Type: Journal article
Publication Details: The FASEB journal, Vol.31(11), pp.4903-4916
DOI: 10.1096/fj.201700533R
PMID: 28729290
PMCID: PMC5636697
NLM abbreviation: FASEB J
ISSN: 1530-6860
eISSN: 1530-6860
Publisher: United States
Grant note: R01 EY024605 / NEI NIH HHS R01 EY026999 / NEI NIH HHS R01 EY022403 / NEI NIH HHS R01 EY021937 / NEI NIH HHS
Language: English
Date published: 11/2017
Academic Unit: Ophthalmology and Visual Sciences
Record Identifier: 9983979961802771

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