PMID- 29610856
OWN - NLM
STAT- MEDLINE
DCOM- 20190128
LR  - 20231213
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Linking)
VI  - 59
IP  - 5
DP  - 2018 Apr 1
TI  - Natural Killer Cell Inhibition by HLA-E Molecules on Induced Pluripotent Stem 
      Cell-Derived Retinal Pigment Epithelial Cells.
PG  - 1719-1731
LID - 10.1167/iovs.17-22703 [doi]
AB  - PURPOSE: To determine whether human induced pluripotent stem (iPS) cell-derived 
      retinal pigment epithelial (RPE) cells (iPS-RPE) can suppress natural killer (NK) 
      cell activation. METHODS: iPS-RPE cells were cocultured with peripheral blood 
      mononuclear cells (PBMCs) or purified NK cells from healthy donors after 
      stimulation with cytokines. To confirm expression of NK cell-specific markers, 
      flow cytometry and quantitative RT-PCR (qRT-PCR) were performed. NK cells (or 
      PBMCs) cocultured with iPS-RPE cells were assessed for proliferation by Ki-67 
      expression with flow cytometry, and NK suppression by RPE cells was assessed for 
      granzyme B production with ELISA. Human leukocyte antigen (HLA) expression 
      including HLA-E on iPS-RPE cells was evaluated with flow cytometry and qRT-PCR. 
      The effect of HLA-E downregulation was also investigated using small interfering 
      RNA (siRNA) systems. Following iPS-RPE cell transplantation in vivo, we evaluated 
      NK cell invasion in the retina with immunohistochemistry. RESULTS: Activated NK 
      cells expressed NK-related markers such as CD16, CD56, and CD11b, and NK cells 
      produced cytotoxic agents such as granzyme B, perforin, and TNF-alpha. Human iPS-RPE 
      cells inhibited cell proliferation and production of these cytotoxic agents by 
      activated NK cells in vitro. iPS-RPE cells constitutively expressed HLA-E and 
      suppressed NK cell activation through an interaction between HLA-E and 
      CD94/NKG2A. Moreover, immunohistochemical evaluation of monkey RPE 
      transplantation into in vivo immune rejection models showed no NK cell invasion 
      in the retina in allografts or xenografts except for one xenografted eye. 
      CONCLUSIONS: Cultured iPS cell-derived RPE cells greatly suppress NK cell 
      activation. Thus, NK cells might be inactivated when exposed to this type of 
      retinal cell.
FAU - Sugita, Sunao
AU  - Sugita S
AD  - Laboratory for Retinal Regeneration, RIKEN Center for Developmental Biology, 
      Kobe, Hyogo, Japan.
FAU - Makabe, Kenichi
AU  - Makabe K
AD  - Laboratory for Retinal Regeneration, RIKEN Center for Developmental Biology, 
      Kobe, Hyogo, Japan.
FAU - Iwasaki, Yuko
AU  - Iwasaki Y
AD  - Laboratory for Retinal Regeneration, RIKEN Center for Developmental Biology, 
      Kobe, Hyogo, Japan.
AD  - Department of Ophthalmology & Visual Science, Tokyo Medical and Dental University 
      Graduate School of Medicine and Dental Sciences, Tokyo, Japan.
FAU - Fujii, Shota
AU  - Fujii S
AD  - Laboratory for Retinal Regeneration, RIKEN Center for Developmental Biology, 
      Kobe, Hyogo, Japan.
AD  - Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.
FAU - Takahashi, Masayo
AU  - Takahashi M
AD  - Laboratory for Retinal Regeneration, RIKEN Center for Developmental Biology, 
      Kobe, Hyogo, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Antigens, CD)
RN  - 0 (Biomarkers)
RN  - 0 (Cytokines)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Ki-67 Antigen)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (beta 2-Microglobulin)
RN  - EC 3.4.21.- (Granzymes)
SB  - IM
MH  - Animals
MH  - Antigens, CD/metabolism
MH  - Biomarkers/metabolism
MH  - Blotting, Western
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Cytokines/metabolism
MH  - Flow Cytometry
MH  - Granzymes/metabolism
MH  - Histocompatibility Antigens Class I/*pharmacology
MH  - Humans
MH  - Immunohistochemistry
MH  - Induced Pluripotent Stem Cells/*cytology
MH  - Ki-67 Antigen/metabolism
MH  - Killer Cells, Natural/*immunology
MH  - Lymphocyte Activation/*drug effects
MH  - Macaca
MH  - RNA, Small Interfering/genetics
MH  - Real-Time Polymerase Chain Reaction
MH  - Retinal Pigment Epithelium/*immunology/transplantation
MH  - Transfection
MH  - beta 2-Microglobulin/genetics
MH  - HLA-E Antigens
EDAT- 2018/04/04 06:00
MHDA- 2019/01/29 06:00
CRDT- 2018/04/04 06:00
PHST- 2018/04/04 06:00 [entrez]
PHST- 2018/04/04 06:00 [pubmed]
PHST- 2019/01/29 06:00 [medline]
AID - 2677968 [pii]
AID - 10.1167/iovs.17-22703 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2018 Apr 1;59(5):1719-1731. doi: 
      10.1167/iovs.17-22703.