Retinal Pigment Epithelial Cells Derived from Induced Pluripotent Stem (iPS) Cells Suppress or Activate T Cells via Costimulatory Signals
Human retinal pigment epithelial (RPE) cells derived from induced pluripotent stem (iPS) cells have immunosuppressive properties. However, RPE cells are also known as immunogenic cells, and they have major histocompatibility complex expression and produce inflammatory proteins, and thus experience i...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2020-09-01
|
Series: | International Journal of Molecular Sciences |
Subjects: | |
Online Access: | https://www.mdpi.com/1422-0067/21/18/6507 |
id |
doaj-a61c8cfdec1d45e593d0d173bfaf0f83 |
---|---|
record_format |
Article |
spelling |
doaj-a61c8cfdec1d45e593d0d173bfaf0f832020-11-25T03:25:46ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-09-01216507650710.3390/ijms21186507Retinal Pigment Epithelial Cells Derived from Induced Pluripotent Stem (iPS) Cells Suppress or Activate T Cells via Costimulatory SignalsSunao Sugita0Yoko Futatsugi1Masaaki Ishida2Ayaka Edo3Masayo Takahashi4Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku Kobe 650-0047, JapanLaboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku Kobe 650-0047, JapanLaboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku Kobe 650-0047, JapanLaboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku Kobe 650-0047, JapanLaboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku Kobe 650-0047, JapanHuman retinal pigment epithelial (RPE) cells derived from induced pluripotent stem (iPS) cells have immunosuppressive properties. However, RPE cells are also known as immunogenic cells, and they have major histocompatibility complex expression and produce inflammatory proteins, and thus experience immune rejection after transplantation. In this study, to confirm the immunological properties of IPS-RPE cells, we examined whether human RPE cells derived from iPS cells could suppress or stimulate inflammatory T cells from uveitis patients via costimulatory signals. We established T cells from patients with active uveitis as target cells and used iPS-RPE cells as effector cells. As a result, cultured iPS-RPE cells inhibited cell proliferation and the production of IFN-γ by activated uveitis CD4<sup>+</sup> T cells, especially Th1-type T cells. In contrast, iPS-RPE cells stimulated T cells of uveitis patients. The iPS-RPE cells constitutively expressed B7-H1/CD274 and B7-DC/CD273, and suppressed the activation of T cells via the PD-1 receptor. iPS-RPE expressed these negative costimulatory molecules, especially when RPE cells were pretreated with recombinant IFN-γ. In addition, iPS-RPE cells also expressed B7-H3/CD276 costimulatory molecules and activated uveitis T cells through the B7-H3-TLT-2 receptor. Thus, cultured iPS-derived retinal cells can suppress or activate inflammatory T cells in vitro through costimulatory interactions.https://www.mdpi.com/1422-0067/21/18/6507iPS cellsretinal pigment epithelial cellsuveitissuppressionstimulationcostimulatory molecules |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sunao Sugita Yoko Futatsugi Masaaki Ishida Ayaka Edo Masayo Takahashi |
spellingShingle |
Sunao Sugita Yoko Futatsugi Masaaki Ishida Ayaka Edo Masayo Takahashi Retinal Pigment Epithelial Cells Derived from Induced Pluripotent Stem (iPS) Cells Suppress or Activate T Cells via Costimulatory Signals International Journal of Molecular Sciences iPS cells retinal pigment epithelial cells uveitis suppression stimulation costimulatory molecules |
author_facet |
Sunao Sugita Yoko Futatsugi Masaaki Ishida Ayaka Edo Masayo Takahashi |
author_sort |
Sunao Sugita |
title |
Retinal Pigment Epithelial Cells Derived from Induced Pluripotent Stem (iPS) Cells Suppress or Activate T Cells via Costimulatory Signals |
title_short |
Retinal Pigment Epithelial Cells Derived from Induced Pluripotent Stem (iPS) Cells Suppress or Activate T Cells via Costimulatory Signals |
title_full |
Retinal Pigment Epithelial Cells Derived from Induced Pluripotent Stem (iPS) Cells Suppress or Activate T Cells via Costimulatory Signals |
title_fullStr |
Retinal Pigment Epithelial Cells Derived from Induced Pluripotent Stem (iPS) Cells Suppress or Activate T Cells via Costimulatory Signals |
title_full_unstemmed |
Retinal Pigment Epithelial Cells Derived from Induced Pluripotent Stem (iPS) Cells Suppress or Activate T Cells via Costimulatory Signals |
title_sort |
retinal pigment epithelial cells derived from induced pluripotent stem (ips) cells suppress or activate t cells via costimulatory signals |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2020-09-01 |
description |
Human retinal pigment epithelial (RPE) cells derived from induced pluripotent stem (iPS) cells have immunosuppressive properties. However, RPE cells are also known as immunogenic cells, and they have major histocompatibility complex expression and produce inflammatory proteins, and thus experience immune rejection after transplantation. In this study, to confirm the immunological properties of IPS-RPE cells, we examined whether human RPE cells derived from iPS cells could suppress or stimulate inflammatory T cells from uveitis patients via costimulatory signals. We established T cells from patients with active uveitis as target cells and used iPS-RPE cells as effector cells. As a result, cultured iPS-RPE cells inhibited cell proliferation and the production of IFN-γ by activated uveitis CD4<sup>+</sup> T cells, especially Th1-type T cells. In contrast, iPS-RPE cells stimulated T cells of uveitis patients. The iPS-RPE cells constitutively expressed B7-H1/CD274 and B7-DC/CD273, and suppressed the activation of T cells via the PD-1 receptor. iPS-RPE expressed these negative costimulatory molecules, especially when RPE cells were pretreated with recombinant IFN-γ. In addition, iPS-RPE cells also expressed B7-H3/CD276 costimulatory molecules and activated uveitis T cells through the B7-H3-TLT-2 receptor. Thus, cultured iPS-derived retinal cells can suppress or activate inflammatory T cells in vitro through costimulatory interactions. |
topic |
iPS cells retinal pigment epithelial cells uveitis suppression stimulation costimulatory molecules |
url |
https://www.mdpi.com/1422-0067/21/18/6507 |
work_keys_str_mv |
AT sunaosugita retinalpigmentepithelialcellsderivedfrominducedpluripotentstemipscellssuppressoractivatetcellsviacostimulatorysignals AT yokofutatsugi retinalpigmentepithelialcellsderivedfrominducedpluripotentstemipscellssuppressoractivatetcellsviacostimulatorysignals AT masaakiishida retinalpigmentepithelialcellsderivedfrominducedpluripotentstemipscellssuppressoractivatetcellsviacostimulatorysignals AT ayakaedo retinalpigmentepithelialcellsderivedfrominducedpluripotentstemipscellssuppressoractivatetcellsviacostimulatorysignals AT masayotakahashi retinalpigmentepithelialcellsderivedfrominducedpluripotentstemipscellssuppressoractivatetcellsviacostimulatorysignals |
_version_ |
1724595941553471488 |