2692-P: Individual Human Beta Cells Secrete Differential Levels of the Proinflammatory Cytokine CXCL10

Introduction and Objective: The exact cause of Type 1 diabetes is not yet known, but recent findings indicate a key role for beta cells in the progression of the disease including inflammatory stress responses. Previous studies have shown that beta cells exhibit subtypes, marked by differences in surface markers, functional insulin secretion, and gene expression. Here, we leveraged microscale hydrogel compartments called Nanovials to determine whether beta cell subtypes exist based on their secretion of CXCL10, a proinflammatory cytokine highly implicated in Type 1 diabetes. Methods: Nanovials allow a user to isolate a single cell and quantify its secreted proteins. Here we discriminated human beta cell subtypes by measuring differential CXCL10 secretion and presence of specific surface markers. Beta cells were induced to secrete CXCL10 via treatment with a cytokine cocktail, and subsequent secretion and surface markers were identified via antibody staining. Results: For beta cells treated with cytokine, we identified subpopulations, noted as “moderate CXCL10 secretors” and “high CXCL10 secretors”. These subpopulations were not present in non-cytokine-treated beta cells, as they did not secrete CXCL10 at all. Amongst CXCL10 secretors, we identified beta cells and non-beta cells, suggesting a potentially important role for alpha or delta cells in CXCL10 secretion within the pancreatic endocrine population. Conclusion: Our results demonstrate that beta cell subtypes can be discriminated solely based on single cell protein secretion, a novel technique in the field. Specifically, varying levels of secreted CXCL10 can be measured. The characterization of immunogenic subtypes allows for deeper understanding of beta cell heterogeneity and its potential role in Type 1 diabetes etiology. Disclosure M. Morin: Other - contractor - intern; Ended; Pfizer Inc. J. Barra: Consultant; Current; Tolerance Bio. A.M. Ladd: None. H. Russ: Other - Advisory panel and consultant, stock holder; Current; Sernova, Corp. Other - Scientific founder, Consultant, Advisory panel, stock holder; Current; Tolerance Bio. Consultant; Current; Guidepoint consulting, Axxon Advisors. Funding NIH (R01 DK1323872-SRA-2023-1313-S-B3-SRA-2023-1367-S-B)