title: γδ T cells as a major source of IL-17 production during age-dependent RPE degeneration.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Texas Medical Branch, Galveston, Texas, United States.
authors.forename: Zhenyang
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Texas Medical Branch, Galveston, Texas, United States.
authors.forename: Pei
authors.initials: P
authors.lastname: Xu
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States.
authors.forename: Zuliang
authors.initials: Z
authors.lastname: Jie
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Texas Medical Branch, Galveston, Texas, United States.
authors.forename: Yiqin
authors.initials: Y
authors.lastname: Zuo
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Texas Medical Branch, Galveston, Texas, United States.
authors.forename: Bo
authors.initials: B
authors.lastname: Yu
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States.
authors.forename: Lynn
authors.initials: L
authors.lastname: Soong
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States.
authors.forename: Jiaren
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Texas Medical Branch, Galveston, Texas, United States.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Texas Medical Branch, Galveston, Texas, United States Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, Texas, United States.
authors.forename: Jiyang
authors.initials: J
authors.lastname: Cai
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005434:Flow Cytometry; D007111:Immunity, Cellular; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D020381:Interleukin-17 / Q000096:biosynthesis*; D008268:Macular Degeneration / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D055213:Retinal Pigment Epithelium / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D041623:Tomography, Optical Coherence / Q000379:methods
chemical_list: D020381:Interleukin-17
keywords: IL-17; T lymphocyte; age-related macular degeneration; inflammation