| Presentation preference | Oral presentation |
| Title | Targeting IFN-γ ameliorates cytotoxic responses in retinal degenerative disease and enhances long-term functional engraftment of hESC-derived RPE cells transplantation |
| Purpose | To investigate the impacts of pro-inflammatory T cells in the etiology of age-related macular degeneration (AMD) pathogenesis. |
| Methods | Flow cytometry was performed to decect the frequencies of different T cell subsets in the PBMCs from AMD patients and healthy controls. Integrative analysis of single-cell RNA-sequencing (scRNA-seq) and proteomic profiling were performed to assess the retinal and peripheral micro-environment of AMD patients. AMD PBMCs primed hESC-RPE cells were used to mimic diseased retinal microenvironment for in vitro and drug screening experiments. |
| Results | Increased Th1 cell frequency was detected in the PBMCs from AMD patients, along with increased infiltration of IFN-γ producing CD4+/CD8+ T lymphocytes as well as NK cells. The results of scRNA-seq and proteomic profiling further confirmed activation of IFN-γ signaling and involvement of T/NK cells in the peripheral blood and retina from AMD patients. IFN-γ could trigger JAK signaling activation and enhance antigen processing and presenting via HLA expression, eventually leading to T/NK cell mediated cytotoxic response. JAK1 signaling FDA approved JAK1/2 inhibitor-ruxolitinib could hinder the cytotoxicity responses and improve the engraftment of hESC-RPE cells into degenerated retina. |
| Conclusion | Our work elucidates the role of IFN-γ in AMD and introduces an approach for suppressing cytotoxicity responses and allograft rejection in an IFN-γ-specific manner, showing potential applications for hESC-derived cell replacement therapy without systemic immune suppression, with a promising view to successful clinical outcomes. |
| Conflict of interest | No |
Authors 1
| Last name | GAO |
| Initials of first name(s) | Y |
| Department | Southwest Hospital，Army Medical University |
| City | Chongqing |
| Country | China |
