| Title: | Macrophage-like iPS-derived Suppressor Cells Reduce Th1-mediated Immune Response to a Retinal Antigen |
| Authors: | Hase, Keitaro Browse this author |
| Namba, Kenichi Browse this author →KAKEN DB |
| Wada, Haruka Browse this author →KAKEN DB |
| Tsuji, Hyuma Browse this author |
| Maeda, Aoi Browse this author |
| Murata, Tomoki Browse this author |
| Otsuka, Ryo Browse this author |
| Iwata, Daiju Browse this author |
| Kanda, Atsuhiro Browse this author |
| Noda, Kousuke Browse this author →KAKEN DB |
| Kitaichi, Nobuyoshi Browse this author |
| Seino, Ken-Ichiro Browse this author →KAKEN DB |
| Ishida, Susumu Browse this author →KAKEN DB |
| Keywords: | Retinal antigen |
| type 1 helper T cells |
| cellular immunity |
| immunosuppression |
| iPS cells |
| Issue Date: | 2-Dec-2021 |
| Publisher: | Taylor & Francis |
| Journal Title: | Current eye research |
| Volume: | 46 |
| Issue: | 12 |
| Start Page: | 1908 |
| End Page: | 1916 |
| Publisher DOI: | 10.1080/02713683.2021.1952605 |
| Abstract: | Purpose To investigate the immunotherapeutic effects of macrophage-like induced pluripotent stem (iPS) cell-derived suppressor cells (SCs) in ocular immune response and experimental autoimmune uveoretinitis (EAU). Methods The genes of Oct3/4, Sox2, Klf4, and c-Myc were transferred to B cells enriched from the spleen cells of C57BL/6 mice by using retrovirus vectors. Transferred B cells were cultured for 17 days to obtain colonies of iPS cells. Through additional steps, iPS-SCs were induced. An antigen-specific T cell proliferation assay was performed with CD4(+) T cells collected from draining lymph nodes of the mice immunized with human interphotoreceptor retinoid-binding protein (hIRBP) peptide and co-cultured with iPS-SCs. Cytokine concentrations in the culture supernatant were examined. Mice were immunized with hIRBP peptide to induce EAU. The iPS-SCs were administered into the mice one day before the induction of EAU. Results The iPS-SCs decreased hIRBP-specific T cell proliferation depending on the number of cells. Productions of tumor necrosis factor-alpha and interferon-gamma were significantly decreased; however, transforming growth factor-beta 1, nitric oxide, interleukin (IL)-13, IL-17A, and IL-17 F levels were elevated in the supernatant when the collected T cells were co-cultured with iPS-SCs. The iPS-SCs had immunosuppressant effects even without cell-to-cell contact, and their effects were non-specific to the antigen preloaded on iPS-SCs. EAU was significantly milder in the mice administered iPS-SCs prior to immunization. Conclusions Macrophage-like iPS-SCs reduced Th1 immune response to a retinal antigen and Th1-mediated EAU in mice. These results showed the possibility of the application of iPS technology to the treatment of noninfectious ocular inflammation, endogenous uveitis, in the future. |
| Rights: | This is an Accepted Manuscript of an article published by Taylor & Francis in Current eye research on 2021/12/02, available online: http://www.tandfonline.com/10.1080/02713683.2021.1952605. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/87439 |
| Appears in Collections: | 北海道大学病院 (Hokkaido University Hospital) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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