Dataset Information

Protective Renalase-deficiency in beta cells shapes immune metabolism and function in autoimmune diabetes

ABSTRACT: Type 1 diabetes (T1D) is caused by the immune-mediated loss of pancreatic beta cells that produce insulin. The latest advances in stem cell (SC)-beta cell differentiation methods have made a cell replacement therapy for T1D feasible. However, recurring autoimmunity would rapidly destroy transplanted SC-beta cells. A promising strategy to overcome immune rejection is to genetically engineer SC-beta cells. We previously identified Renalase (Rnls) as a novel target for beta cell protection. Here we show that Rnls deletion endows beta cells with the capacity to modulate the metabolism and function of immune cells within the local graft microenvironment. We used flow cytometry and single-cell RNA sequencing to characterize beta cell graft-infiltrating immune cells in a mouse model for T1D. Loss of Rnls within transplanted beta cells affected both the composition and the transcriptional profile of infiltrating immune cells in favor of an anti-inflammatory phenotype with decreased antigen presenting capacity. We propose that changes in beta cell metabolism mediate local immune regulation and that this feature could be exploited for therapeutic goals.

ORGANISM(S): Mus musculus

PROVIDER: GSE226361 | GEO | 2024/02/27

REPOSITORIES: GEO

ACCESS DATA

Similar Datasets

Project description:Immune privileged Sertoli cells (SC) survive when transplanted across immunological barriers and prolong the survival of co-transplanted allogeneic and xenogeneic cells in rodent models. However, the mechanism for this survival and protection remains unresolved. We have recently identified a mouse Sertoli cell line (MSC-1) that lacks some of the immunoprotective abilities associated with primary SC. The objective of this study was to compare the survival and gene expression profiles of primary SC and MSC-1 cells to identify factors or immune-related pathways potentially important for SC immune privilege. Primary SC or MSC-1 cells were transplanted as allografts to the renal subcapsular area of naïve BALB/c mice and cell survival was analyzed by immunohistochemistry. Additionally, transcriptome differences were investigated by microarray and pathway analyses. While primary SC were detected within the grafts with 100% graft survival throughout the 20-day study, MSC-1 cells w ere rejected between 11 and 14 days with 0% graft survival at 20 days post-transplantation. Microarray analysis identified 3198 genes that were differentially expressed with a ± 4-fold or higher level in primary SC. Cluster and pathway analyses indicate that the mechanism of SC immune privilege is likely complex with multiple immune modulators being involved such as immunosuppressive cytokines and complement inhibitors, lipid mediators for controlling inflammation, and junctional molecules that control leukocyte movement in and out of the immune privileged space. Further study of these immune modulators will increase our understanding of SC immune privilege and in the long-term lead to improvements in transplantation success. We conducted microarray and pathway analyses to identify genes and immune-related pathways differentially regulated by aggregated primary Sertoli cells and MSC-1 cell line. Aggregated 19 to 20-day mice primary Sertoli cells and MSC-1 cell line were used to determine the global transcriptome differences important for the survival and protection of transplanted cells.

Dataset Information

Protective Renalase-deficiency in beta cells shapes immune metabolism and function in autoimmune diabetes

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure