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

Powell, Wendy E., Hanna, Stephanie J., Hocter, Claire N., Robinson, Emma, Davies, Joanne, Dunseath, Gareth J., Luzio, Stephen, Farewell, Daniel, Wen, Li, Dayan, Colin M., Price, David A., Ladell, Kristin and Wong, F. Susan 2018. Loss of CXCR3 expression on memory B cells in individuals with long-standing type 1 diabetes. Diabetologia 61 (8) , 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: Medicine
Publisher: Springer Verlag (Germany)
ISSN: 0012-186X
Date of First Compliant Deposit: 29 June 2018
Date of Acceptance: 27 April 2018
Last Modified: 29 May 2019 23:20
URI: http://orca.cf.ac.uk/id/eprint/112868

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