Retinal Pigment Epithelial Cells Derived from Induced Pluripotent Stem (iPS) Cells Suppress or Activate T Cells via Costimulatory Signals.

Tytuł:: Retinal Pigment Epithelial Cells Derived from Induced Pluripotent Stem (iPS) Cells Suppress or Activate T Cells via Costimulatory Signals.
Autorzy:: Sugita S; 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.
Futatsugi Y; 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.
Ishida M; Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku Kobe 650-0047, Japan.
Edo A; 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.
Takahashi M; 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.
Źródło:: International journal of molecular sciences [Int J Mol Sci] 2020 Sep 05; Vol. 21 (18). Date of Electronic Publication: 2020 Sep 05.
Typ publikacji:: Journal Article
Język:: English
Imprint Name(s):: Original Publication: Basel, Switzerland : MDPI, [2000-
MeSH Terms:: Costimulatory and Inhibitory T-Cell Receptors/*immunology
Retinal Pigment Epithelium/*metabolism
T-Lymphocytes/*physiology
B7 Antigens/metabolism ; B7-H1 Antigen/metabolism ; CD4-Positive T-Lymphocytes/immunology ; Cell Proliferation/drug effects ; Cells, Cultured ; Costimulatory and Inhibitory T-Cell Receptors/metabolism ; Epithelial Cells/metabolism ; Flow Cytometry ; Humans ; Induced Pluripotent Stem Cells/cytology ; Induced Pluripotent Stem Cells/physiology ; Interferon-gamma/metabolism ; Interleukin-2/metabolism ; Lymphocyte Activation/immunology ; Programmed Cell Death 1 Ligand 2 Protein/metabolism ; Programmed Cell Death 1 Receptor/metabolism ; Retinal Pigment Epithelium/immunology ; Retinal Pigment Epithelium/physiology ; Retinal Pigments/metabolism ; Uveitis/immunology ; Uveitis/metabolism
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Grant Information:: M0115025 Japan Agency for Medical Research and Development
Contributed Indexing:: Keywords: costimulatory molecules; iPS cells; retinal pigment epithelial cells; stimulation; suppression; uveitis
Substance Nomenclature:: 0 (B7 Antigens)
0 (B7-H1 Antigen)
0 (CD274 protein, human)
0 (CD276 protein, human)
0 (Costimulatory and Inhibitory T-Cell Receptors)
0 (Interleukin-2)
0 (PDCD1LG2 protein, human)
0 (Programmed Cell Death 1 Ligand 2 Protein)
0 (Programmed Cell Death 1 Receptor)
0 (Retinal Pigments)
82115-62-6 (Interferon-gamma)
Entry Date(s):: Date Created: 20200909 Date Completed: 20210224 Latest Revision: 20210224
Update Code:: 20240105
PubMed Central ID:: PMC7554762
DOI:: 10.3390/ijms21186507
PMID:: 32899567
: Czasopismo naukowe

Pełny tekst

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.

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