γδ T cells as a major source of IL-17 production during age-dependent RPE degeneration

Zhenyang Zhao, Pei Xu, Zuliang Jie, Yiqin Zuo, Bo Yu, Lynn Soong, Jiaren Sun, Yan Chen, Jiyang Cai

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

PURPOSE: Chronic inflammation is a key factor contributing to the progression of age-related macular degeneration (AMD). The goals of the current study were to develop an improved mouse model with retinal pathologic features similar to those of AMD and to characterize the immunoreactive cells in the outer retina and choroid during degeneration of the retinal pigment epithelium (RPE).

METHODS: Mice deficient in nuclear erythroid 2-related factor 2 (Nrf2) at 12 months of age were fed a high-fat, cholesterol-rich diet for up to 16 weeks. Ocular phenotype was monitored by optical coherence tomography (OCT) and scanning laser ophthalmoscopy (SLO) in live animals, and was further validated by retinal histopathology. Immunofluorescence staining of either cryosections or RPE flat mounts was used to define immunoreactive cells. Flow cytometry analyses were further performed to define the subsets of intraocular T lymphocytes.

RESULTS: After 16 weeks on a high-fat (HF) diet, 58% of the eyes from Nrf2-/- mice had progression of retinal lesions. Major histocompatibility complex class II (MHC II)-positive microglia, FoxP3+ regulatory T cells (Tregs), and CD3+ IL-17-producing T cells were detected in either the retina or sub-RPE space. Flow cytometry analyses further revealed that most of the IL-17-producing cells were CD3+ CD4- TCRγδ+ cells.

CONCLUSIONS: The results suggest that the T cell-mediated immune responses played important roles in controlling the progression of AMD-like phenotype in Nrf2-deficient mice.

Original languageEnglish (US)
Pages (from-to)6580-6589
Number of pages10
JournalInvestigative Ophthalmology and Visual Science
Volume55
Issue number10
DOIs
StatePublished - 2014

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Interleukin-17
Retinal Pigment Epithelium
Macular Degeneration
T-Lymphocytes
Retina
Flow Cytometry
Phenotype
Ophthalmoscopy
Choroid
Optical Coherence Tomography
Microglia
T-Lymphocyte Subsets
High Fat Diet
Regulatory T-Lymphocytes
Major Histocompatibility Complex
Fluorescent Antibody Technique
Lasers
Fats
Cholesterol
Staining and Labeling

Keywords

  • age-related macular degeneration
  • IL-17
  • inflammation
  • T lymphocyte

ASJC Scopus subject areas

  • Medicine(all)

Cite this

γδ T cells as a major source of IL-17 production during age-dependent RPE degeneration. / Zhao, Zhenyang; Xu, Pei; Jie, Zuliang; Zuo, Yiqin; Yu, Bo; Soong, Lynn; Sun, Jiaren; Chen, Yan; Cai, Jiyang.

In: Investigative Ophthalmology and Visual Science, Vol. 55, No. 10, 2014, p. 6580-6589.

Research output: Contribution to journalArticle

Zhao, Zhenyang ; Xu, Pei ; Jie, Zuliang ; Zuo, Yiqin ; Yu, Bo ; Soong, Lynn ; Sun, Jiaren ; Chen, Yan ; Cai, Jiyang. / γδ T cells as a major source of IL-17 production during age-dependent RPE degeneration. In: Investigative Ophthalmology and Visual Science. 2014 ; Vol. 55, No. 10. pp. 6580-6589.
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AU - Jie, Zuliang

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AU - Yu, Bo

AU - Soong, Lynn

AU - Sun, Jiaren

AU - Chen, Yan

AU - Cai, Jiyang

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N2 - PURPOSE: Chronic inflammation is a key factor contributing to the progression of age-related macular degeneration (AMD). The goals of the current study were to develop an improved mouse model with retinal pathologic features similar to those of AMD and to characterize the immunoreactive cells in the outer retina and choroid during degeneration of the retinal pigment epithelium (RPE).METHODS: Mice deficient in nuclear erythroid 2-related factor 2 (Nrf2) at 12 months of age were fed a high-fat, cholesterol-rich diet for up to 16 weeks. Ocular phenotype was monitored by optical coherence tomography (OCT) and scanning laser ophthalmoscopy (SLO) in live animals, and was further validated by retinal histopathology. Immunofluorescence staining of either cryosections or RPE flat mounts was used to define immunoreactive cells. Flow cytometry analyses were further performed to define the subsets of intraocular T lymphocytes.RESULTS: After 16 weeks on a high-fat (HF) diet, 58% of the eyes from Nrf2-/- mice had progression of retinal lesions. Major histocompatibility complex class II (MHC II)-positive microglia, FoxP3+ regulatory T cells (Tregs), and CD3+ IL-17-producing T cells were detected in either the retina or sub-RPE space. Flow cytometry analyses further revealed that most of the IL-17-producing cells were CD3+ CD4- TCRγδ+ cells.CONCLUSIONS: The results suggest that the T cell-mediated immune responses played important roles in controlling the progression of AMD-like phenotype in Nrf2-deficient mice.

AB - PURPOSE: Chronic inflammation is a key factor contributing to the progression of age-related macular degeneration (AMD). The goals of the current study were to develop an improved mouse model with retinal pathologic features similar to those of AMD and to characterize the immunoreactive cells in the outer retina and choroid during degeneration of the retinal pigment epithelium (RPE).METHODS: Mice deficient in nuclear erythroid 2-related factor 2 (Nrf2) at 12 months of age were fed a high-fat, cholesterol-rich diet for up to 16 weeks. Ocular phenotype was monitored by optical coherence tomography (OCT) and scanning laser ophthalmoscopy (SLO) in live animals, and was further validated by retinal histopathology. Immunofluorescence staining of either cryosections or RPE flat mounts was used to define immunoreactive cells. Flow cytometry analyses were further performed to define the subsets of intraocular T lymphocytes.RESULTS: After 16 weeks on a high-fat (HF) diet, 58% of the eyes from Nrf2-/- mice had progression of retinal lesions. Major histocompatibility complex class II (MHC II)-positive microglia, FoxP3+ regulatory T cells (Tregs), and CD3+ IL-17-producing T cells were detected in either the retina or sub-RPE space. Flow cytometry analyses further revealed that most of the IL-17-producing cells were CD3+ CD4- TCRγδ+ cells.CONCLUSIONS: The results suggest that the T cell-mediated immune responses played important roles in controlling the progression of AMD-like phenotype in Nrf2-deficient mice.

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