title: A2E Suppresses Regulatory Function of RPE Cells in Th1 Cell Differentiation Via Production of IL-1β and Inhibition of PGE2.
abstract: OBJECTIVE
  Inflammatory status of RPE cells induced by A2E is essential in the development of AMD. Recent research indicated T-cell immunity was involved in the pathological progression of AMD. This study was designed to investigate how A2E suppresses immunoregulatory function of RPE cells in T-cell immunity in vitro.
  
  
  METHODS
  Mouse RPE cells or human ARPE19 cells were stimulated with A2E, and co-cultured with naïve T cells under Th1, Th2, Th17, and regulatory T cell (Treg) polarization conditions. The intracellular cytokines or transcript factors of the induced T-cells subset were detected with flow cytometer and qRT-PCR. The ROS levels were detected, and the factors and possible pathways involved in the A2E-laden RPE cells were analyzed through neutralization antibody of IL-1β and inhibitors of related pathways.
  
  
  RESULTS
  The A2E reduced regulatory function of RPE cells in Treg differentiation. The A2E-laden RPE cells promoted polarization of Th1 cells in vitro, but not Th2 or Th17 differentiation. The A2E induced RPE cells to release inflammatory cytokines and ROS, but PGE2 production was inhibited. Through neutralization of IL-1β or inhibition of COX2-PGE2 pathways, A2E-laden RPE cells expressed reduced effect in inducing Th1 cells.
  
  
  CONCLUSIONS
  The A2E inhibited regulatory function of RPE cells in suppressing Th1 cell immunity in vitro through production of IL-1β and inhibition of PGE2. Our data indicate that A2E could suppress immunoregulatory function of RPE cells and adaptive immunity might play a role in the immune pathogenesis of AMD.
authors.affiliation: Department of Ophthalmology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China 2Research Center for Translational Medicine and Shanghai Heart Failure Research Center, Shanghai East Hos.
authors.forename: Qian
authors.initials: Q
authors.lastname: Shi
authors.affiliation: Department of Ophthalmology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Qiu
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Research Center for Translational Medicine and Shanghai Heart Failure Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Research Center for Translational Medicine and Shanghai Heart Failure Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Research Center for Translational Medicine and Shanghai Heart Failure Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Fan
authors.affiliation: Department of Ophthalmology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Fenghua
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Haiyun
authors.initials: H
authors.lastname: Liu
authors.affiliation: School of Biology and Agriculture, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Ophthalmology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China 4Shanghai Key Laboratory of Fundus Disease, Shanghai, People's Republic of China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Sun
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D066298:In Vitro Techniques; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000378:metabolism*; D008213:Lymphocyte Activation; D008268:Macular Degeneration / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D055213:Retinal Pigment Epithelium / Q000473:pathology*; D012176:Retinoids / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D018417:Th1 Cells / Q000378:metabolism*
chemical_list: C112040:A2-E (N-retinylidene-N-retinylethanolamine); D053583:Interleukin-1beta; D012176:Retinoids