Capacity of Retinal Ganglion Cells Derived from Human Induced Pluripotent Stem Cells to Suppress T-Cells
Abstract
:1. Introduction
2. Results
2.1. Preparation of iPSC-RGCs
2.2. Immunogenicity of iPSC-RGCs Assessed with HLA Class I, Class II, and Co-Stimulatory Molecules
2.3. Human iPSC-RGCs are able to Suppress Immune Cell Activation In Vitro
2.4. Elucidating of the Immunosuppressive Mechanism of iPSC-RGCs
2.5. Detection of TGF-β in iPSC-RGCs
2.6. Role of TGF-β in T-Cell Suppression by iPSC-RGCs
3. Discussion
4. Materials and Methods
4.1. Establishment of Human iPSCs
4.2. Preparation, Isolation, and Culture of iPSC-RGCs
4.3. Flow Cytometry
4.4. Quantitative RT-PCR
4.5. IHC and ICC
4.6. MLR Assay with iPSC-RGCs
4.7. T-cell Proliferation Assay with iPSC-RGCs
4.8. Expression Analysis with Microarray
4.9. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
FACS | fluorescence-activated cell sorting |
HLA | human leukocyte antigen |
ICC | Immunocytochemistry |
IHC | Immunohistochemistry |
iPSCs | induced pluripotent stem cells |
MLR | mixed lymphocyte reaction |
NK | natural killer |
PBMCs | peripheral blood mononuclear cells |
RGCs | retinal ganglion cells |
RPEs | retinal pigment epithelial cells |
RT-PCR | reverse transcription-polymerase chain reaction |
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Accession Number | Gene Description | Abbreviations | Signal Log2 Ratio | ||
---|---|---|---|---|---|
Signal in iPSC-RGCs | vs. iPSCs | vs. PBMCs | |||
MHC Class I and Class II | |||||
NM_001242758 | major histocompatibility complex, class I, A | HLA-A | 56.74 | −2.60 | −7.91 |
ENST00000412585 | major histocompatibility complex, class I, B | HLA-B | 130.96 | −2.00 | −8.48 |
NM_001243042 | major histocompatibility complex, class I, C | HLA-C | 134.83 | −3.20 | −8.04 |
NM_001242525 | major histocompatibility complex, class II, DP alpha 1 | HLA-DPA1 | 64.49 | −0.79 | −8.87 |
NM_002121 | major histocompatibility complex, class II, DP beta 1 | HLA-DPB1 | 71.71 | −3.08 | −9.16 |
NM_002122 | major histocompatibility complex, class II, DQ alpha 1 | HLA-DQA1 | 30.59 | −0.11 | −9.89 |
OTTHUMT00000076179 | major histocompatibility complex, class II, DQ alpha 2 | HLA-DQA2 | 69.39 | 0.01 | −5.88 |
NM_001243961 | major histocompatibility complex, class II, DQ beta 1 | HLA-DQB1 | 44.16 | −0.86 | −6.94 |
ENST00000411527 | major histocompatibility complex, class II, DQ beta 2 | HLA-DQB2 | 223.91 | −0.52 | −2.14 |
NM_019111 | major histocompatibility complex, class II, DR alpha | HLA-DRA | 34.59 | −1.70 | −11.94 |
NM_001243965 | major histocompatibility complex, class II, DR beta 1 | HLA-DRB1 | 44.85 | −3.81 | −10.23 |
NM_002125 | major histocompatibility complex, class II, DR beta 5 | HLA-DRB5 | 30.10 | −0.98 | −10.77 |
Co-stimulatory Molecules | |||||
NM_001250 | CD40 molecule, TNF receptor superfamily member 5 | CD40 | 29.43 | −2.27 | −5.70 |
NM_005191 | CD80 molecule | CD80/B7-1 | 23.80 | 0.06 | −4.26 |
NM_001206924 | CD86 molecule | CD86/B7-2 | 12.31 | −0.53 | −6.30 |
NM_001267706 | CD274 molecule | CD274/B7-H1/PD-L1 | 149.33 | 2.33 | −4.57 |
NM_001024736 | CD276 molecule | CD276/B7-H3 | 473.67 | −0.96 | 2.16 |
NM_025239 | programmed cell death 1 ligand 2 | PDCD1LG2/PD-L2/B7-DC | 26.47 | 1.13 | −3.39 |
NM_001283050 | inducible T-cell co-stimulator ligand | ICOSLG/B7-H2 | 61.92 | 0.00 | 0.00 |
NM_001253849 | V-set domain containing T-cell activation inhibitor 1 | VTCN1/B7-H4 | 39.01 | 0.42 | 0.49 |
NM_022153 | chromosome 10 open reading frame 54 | C10orf54/VISTA/B7-H5 | 67.94 | 0.00 | −0.77 |
NM_003327 | tumor necrosis factor receptor superfamily, member 4 | TNFRSF4/OX40L | 26.44 | 0.68 | −2.68 |
NM_001252 | CD70 molecule | CD70 | 13.67 | 0.19 | −4.81 |
NM_001297605 | tumor necrosis factor receptor superfamily, member 14 | TNFRSF14/HVEM | 75.79 | 0.51 | −2.90 |
NM_005092 | tumor necrosis factor (ligand) superfamily, member 18 | TNFSF18/GITRL | 9.20 | −0.40 | −0.55 |
NM_003811 | tumor necrosis factor (ligand) superfamily, member 9 | TNFSF9/4-1BBL/CD137L | 240.76 | −0.15 | −0.15 |
Cytokines and Other Inhibitory Factors/Molecules | |||||
NM_000660 | transforming growth factor beta 1 | TGFB1 | 453.15 | 2.71 | −3.85 |
NM_001135599 | transforming growth factor beta 2 | TGFB2 | 20563.82 | 3.85 | 7.86 |
NM_003239 | transforming growth factor beta 3 | TGFB3 | 30.27 | 0.22 | 0.16 |
NM_000639 | Fas ligand (TNF superfamily, member 6) | FASLG | 24.71 | −0.24 | −2.87 |
NM_004878 | prostaglandin E synthase | PTGES | 171.18 | 0.52 | 0.67 |
NM_001256335 | prostaglandin E synthase 2 | PTGES2 | 234.85 | −0.57 | −0.54 |
NM_000572 | interleukin 10 | IL10 | 19.01 | −0.20 | −2.77 |
NM_002164 | indoleamine 2,3-dioxygenase 1 | IDO1 | 37.34 | −4.22 | −8.23 |
NM_194294 | indoleamine 2,3-dioxygenase 2 | IDO2 | 43.79 | −0.31 | −0.31 |
NM_003381 | vasoactive intestinal peptide | VIP | 25.96 | 0.19 | 0.00 |
NM_002415 | macrophage migration inhibitory factor | MIF | 6137.52 | −0.89 | −0.93 |
NM_002389 | CD46 molecule, complement regulatory protein | CD46 | 3081.43 | −0.78 | −0.35 |
NM_000574 | CD55 molecule, decay accelerating factor for complement | CD55 | 2793.51 | −1.37 | −1.95 |
NM_000611 | CD59 molecule, complement regulatory protein | CD59 | 10117.89 | 1.88 | 1.49 |
NM_003246 | thrombospondin 1 | THBS1/TSP-1 | 10138.58 | 5.59 | 7.24 |
NM_001048 | somatostatin | SST | 959.93 | 5.88 | 5.90 |
NM_000577 | interleukin 1 receptor antagonist | IL1RN | 17.64 | 0.26 | −5.78 |
NM_001777 | CD47 molecule | CD47 | 3346.94 | 1.88 | −1.03 |
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Edo, A.; Sugita, S.; Futatsugi, Y.; Sho, J.; Onishi, A.; Kiuchi, Y.; Takahashi, M. Capacity of Retinal Ganglion Cells Derived from Human Induced Pluripotent Stem Cells to Suppress T-Cells. Int. J. Mol. Sci. 2020, 21, 7831. https://doi.org/10.3390/ijms21217831
Edo A, Sugita S, Futatsugi Y, Sho J, Onishi A, Kiuchi Y, Takahashi M. Capacity of Retinal Ganglion Cells Derived from Human Induced Pluripotent Stem Cells to Suppress T-Cells. International Journal of Molecular Sciences. 2020; 21(21):7831. https://doi.org/10.3390/ijms21217831
Chicago/Turabian StyleEdo, Ayaka, Sunao Sugita, Yoko Futatsugi, Junki Sho, Akishi Onishi, Yoshiaki Kiuchi, and Masayo Takahashi. 2020. "Capacity of Retinal Ganglion Cells Derived from Human Induced Pluripotent Stem Cells to Suppress T-Cells" International Journal of Molecular Sciences 21, no. 21: 7831. https://doi.org/10.3390/ijms21217831