Loss of CXCR3 expression on memory B cells in individuals with long-standing type 1 diabetes

Powell, Wendy E. ORCID: https://orcid.org/0000-0002-4670-1406, Hanna, Stephanie J., Hocter, Claire N., Robinson, Emma, Davies, Joanne, Dunseath, Gareth J., Luzio, Stephen, Farewell, Daniel ORCID: https://orcid.org/0000-0002-8871-1653, Wen, Li, Dayan, Colin M. ORCID: https://orcid.org/0000-0002-6557-3462, Price, David A. ORCID: https://orcid.org/0000-0001-9416-2737, Ladell, Kristin ORCID: https://orcid.org/0000-0002-9856-2938 and Wong, F. Susan ORCID: https://orcid.org/0000-0002-2812-8845 2018. Loss of CXCR3 expression on memory B cells in individuals with long-standing type 1 diabetes. Diabetologia 61 , pp. 1794-1803. 10.1007/s00125-018-4651-x

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Abstract

Aims/hypothesis Islet-specific autoantibodies can predict the development of type 1 diabetes. However, it remains unclear if B cells, per se, contribute to the causal pancreatic immunopathology. We aimed to identify phenotypic signatures of disease progression among naive and memory B cell subsets in the peripheral blood of individuals with type 1 diabetes. Methods A total of 69 participants were recruited across two separate cohorts, one for discovery purposes and the other for validation purposes. Each cohort comprised two groups of individuals with type 1 diabetes (one with newly diagnosed type 1 diabetes and the other with long-standing type 1 diabetes) and one group of age- and sex-matched healthy donors. The phenotypic characteristics of circulating naive and memory B cells were investigated using polychromatic flow cytometry, and serum concentrations of various chemokines and cytokines were measured using immunoassays. Results A disease-linked phenotype was detected in individuals with long-standing type 1 diabetes, characterised by reduced C-X-C motif chemokine receptor 3 (CXCR3) expression on switched (CD27+IgD−) and unswitched (CD27intermediateIgD+) memory B cells. These changes were associated with raised serum concentrations of B cell activating factor and of the CXCR3 ligands, chemokine (C-X-C motif) ligand (CXCL)10 and CXCL11. A concomitant reduction in CXCR3 expression was also identified on T cells. Conclusions/interpretation Our data reveal a statistically robust set of abnormalities that indicate an association between type 1 diabetes and long-term dysregulation of a chemokine ligand/receptor system that controls B cell migration.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine
Additional Information:	This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Publisher:	Springer Verlag
ISSN:	0012-186X
Date of First Compliant Deposit:	29 June 2018
Date of Acceptance:	27 April 2018
Last Modified:	11 Oct 2023 20:39
URI:	https://orca.cardiff.ac.uk/id/eprint/112868

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