CXCR3 expression on antigen experienced B-cells is systemically dysregulated in type 1 diabetes

Boldison, Joanne, Leete, Pia, Robinson, Emma J., Powell, Wendy ORCID: https://orcid.org/0000-0002-4670-1406, Davies, Joanne, McMullan, Conor, Walker, Sophie L., Morgan, Noel G., Hanna, Stephanie J. and Wong, F. Susan ORCID: https://orcid.org/0000-0002-2812-8845 2025. CXCR3 expression on antigen experienced B-cells is systemically dysregulated in type 1 diabetes. Diabetologia Item availability restricted.

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Abstract

Aims: The chemokine receptor CXCR3 is a key chemoattractant molecule which facilitates the migration of activated T-cells to the pancreas, leading to beta cell death. In this study we interrogate CXCR3 responses in B-cells in type 1 diabetes progression. Methods: Peripheral blood samples were obtained from individuals with recent-onset and long-duration type 1 diabetes, age- and sex- matched to healthy donors. We isolated peripheral blood mononuclear cells (PBMCs) and examined changes in CXCR3 expression on lymphocytes in donors, performing multiparameter flow cytometry and functional cell culture assays. Human post-mortem pancreatic tissue was obtained from the Exeter Archival Diabetes Biobank (EADB). Immunofluorescence staining was used to assess CXCR3 expression in pancreatic tissues. Results: We observed reduced CXCR3 on antigen-experienced B-cells in individuals with a long-duration of type 1 diabetes, although B-cells remained responsive to IFNg. In individuals who were recently diagnosed, IFNg treatment resulted in increased CXCR3 expression, compared to B-cells from control individuals. B-cells in the pancreas recovered post-mortem from young recent-onset donors, lacked CXCR3 expression, but co-staining to detect CD8+ T-cells revealed a CXCR3+CD20+CD8+ T-cell population, with their circulating counterpart showing increased CXCR3 expression. Conclusions: We conclude that the CXCR3 response in antigen-experienced B-cells is dysregulated during the progression of type 1 diabetes. CXCR3 expression is limited in CD20+ B cells in the pancreas from recent-onset individuals diagnosed with type 1 diabetes under 7 years of age, but evident on CD8+ T-cells that express CD20

Item Type:	Article
Status:	In Press
Schools:	Schools > Medicine
Publisher:	Springer
ISSN:	0012-186X
Date of First Compliant Deposit:	5 September 2025
Date of Acceptance:	5 September 2025
Last Modified:	05 Sep 2025 14:38
URI:	https://orca.cardiff.ac.uk/id/eprint/180940

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