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
10.1007/s00125-025-06608-y
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Abstract
Aims/hypothesis The chemokine receptor C-X-C chemokine receptor type 3 (CXCR3) is a key chemoattractant molecule that facilitates the migration of activated T cells to the pancreas, leading to beta cell death. In this study, we investigated CXCR3 responses in B cells during type 1 diabetes progression. Methods Peripheral blood samples were obtained from individuals with recent-onset and long-duration type 1 diabetes, who were age- and sex-matched to non-diabetic donors. We isolated peripheral blood mononuclear cells (PBMCs) and examined changes in CXCR3 expression on lymphocytes from donors, performing multiparameter flow cytometry and functional cell culture assays. Human post-mortem pancreatic tissue was obtained from the Exeter Archival Diabetes Biobank. Immunofluorescence staining was used to assess CXCR3 expression in pancreatic tissues. Results We observed reduced CXCR3 expression on antigen-experienced B cells in individuals with a long duration of type 1 diabetes, although B cells remained responsive to IFNγ. In individuals who were recently diagnosed, IFNγ treatment resulted in increased CXCR3 expression compared with B cells from non-diabetic donors. B cells in pancreases that were 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/interpretation 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 pancreases 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 |
|---|---|
| Date Type: | Published Online |
| 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: | 01 Dec 2025 11:50 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/180940 |
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