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Retinal Pigment Epithelial Cells Derived from Induced Pluripotent Stem (iPS) Cells Suppress or Activate T Cells via Costimulatory Signals.
Int J Mol Sci. 2020 Sep 05; 21(18)IJ

Abstract

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+ 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.

Authors+Show Affiliations

Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku Kobe 650-0047, Japan. Department of Ophthalmology, Kobe City Eye Hospital, 2-1-8 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan.Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku Kobe 650-0047, Japan. Department of Ophthalmology, Kobe City Eye Hospital, 2-1-8 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan.Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku Kobe 650-0047, Japan.Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku Kobe 650-0047, Japan. Department of Ophthalmology and Visual Science, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku Kobe 650-0047, Japan. Department of Ophthalmology, Kobe City Eye Hospital, 2-1-8 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32899567

Citation

Sugita, Sunao, et al. "Retinal Pigment Epithelial Cells Derived From Induced Pluripotent Stem (iPS) Cells Suppress or Activate T Cells Via Costimulatory Signals." International Journal of Molecular Sciences, vol. 21, no. 18, 2020.
Sugita S, Futatsugi Y, Ishida M, et al. Retinal Pigment Epithelial Cells Derived from Induced Pluripotent Stem (iPS) Cells Suppress or Activate T Cells via Costimulatory Signals. Int J Mol Sci. 2020;21(18).
Sugita, S., Futatsugi, Y., Ishida, M., Edo, A., & Takahashi, M. (2020). Retinal Pigment Epithelial Cells Derived from Induced Pluripotent Stem (iPS) Cells Suppress or Activate T Cells via Costimulatory Signals. International Journal of Molecular Sciences, 21(18). https://doi.org/10.3390/ijms21186507
Sugita S, et al. Retinal Pigment Epithelial Cells Derived From Induced Pluripotent Stem (iPS) Cells Suppress or Activate T Cells Via Costimulatory Signals. Int J Mol Sci. 2020 Sep 5;21(18) PubMed PMID: 32899567.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Retinal Pigment Epithelial Cells Derived from Induced Pluripotent Stem (iPS) Cells Suppress or Activate T Cells via Costimulatory Signals. AU - Sugita,Sunao, AU - Futatsugi,Yoko, AU - Ishida,Masaaki, AU - Edo,Ayaka, AU - Takahashi,Masayo, Y1 - 2020/09/05/ PY - 2020/08/18/received PY - 2020/08/31/revised PY - 2020/09/01/accepted PY - 2020/9/9/entrez PY - 2020/9/10/pubmed PY - 2021/2/25/medline KW - costimulatory molecules KW - iPS cells KW - retinal pigment epithelial cells KW - stimulation KW - suppression KW - uveitis JF - International journal of molecular sciences JO - Int J Mol Sci VL - 21 IS - 18 N2 - 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+ 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. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/32899567/Retinal_Pigment_Epithelial_Cells_Derived_from_Induced_Pluripotent_Stem__iPS__Cells_Suppress_or_Activate_T_Cells_via_Costimulatory_Signals_ L2 - https://www.mdpi.com/resolver?pii=ijms21186507 DB - PRIME DP - Unbound Medicine ER -