<strong>Protective </strong><em><strong>Renalase</strong></em><strong>-deficiency in beta cells shapes immune metabolism and function in autoimmune diabetes</strong>

• DOI: 10.2337/figshare.22898705.v1
• Publication Date: 2023-05-22T20:19:27Z
• Authors: Kevin Bode; Tara MacDonald; Taylor Stewart; Bryhan Mendez; Erica P. Cai; Noelle Morrow; Yu-Chi Lee; Peng Yi; Stephan Kissler

<p>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 <em>Renalase </em>(<em>Rnls</em>) as a novel target for beta cell protection. Here we show that <em>Rnls </em>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 <em>Rnls</em> within transplanted beta cells affected both the composition and the transcriptional profile of infiltrating immune cells in favor of an anti-inflammatory profile 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. </p>