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In this study, we investigated CXCR3 responses in B\u00a0cells during type 1 diabetes progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We observed reduced CXCR3 expression on antigen-experienced B\u00a0cells in individuals with a long duration of type 1 diabetes, although B\u00a0cells remained responsive to IFN\u03b3. In individuals who were recently diagnosed, IFN\u03b3 treatment resulted in increased CXCR3 expression compared with B\u00a0cells from non-diabetic donors. B\u00a0cells in pancreases that were recovered post-mortem from young recent-onset donors lacked CXCR3 expression, but co-staining to detect CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells revealed a CXCR3\n                      <jats:sup>+<\/jats:sup>\n                      CD20\n                      <jats:sup>+<\/jats:sup>\n                      CD8\n                      <jats:sup>+<\/jats:sup>\n                      T\u00a0cell population, with their circulating counterpart showing increased CXCR3 expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\/interpretation<\/jats:title>\n                    <jats:p>\n                      We conclude that the CXCR3 response in antigen-experienced B\u00a0cells is dysregulated during the progression of type 1 diabetes. CXCR3 expression is limited in CD20\n                      <jats:sup>+<\/jats:sup>\n                      B\u00a0cells in pancreases from recent-onset individuals diagnosed with type 1 diabetes under 7 years of age, but evident on CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells that express CD20.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1007\/s00125-025-06608-y","type":"journal-article","created":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T10:19:27Z","timestamp":1763806767000},"page":"451-465","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["CXCR3 expression on antigen-experienced B\u00a0cells is systemically dysregulated in type 1 diabetes"],"prefix":"10.1007","volume":"69","author":[{"given":"Joanne","family":"Boldison","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pia","family":"Leete","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma J.","family":"Robinson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendy","family":"Powell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanne","family":"Davies","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Conor","family":"McMullan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophie L.","family":"Walker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noel G.","family":"Morgan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie J.","family":"Hanna","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F. 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We thank J. Pearson at Cardiff University for valuable comments on this study.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Acknowledgements"}},{"value":"Data are available from the corresponding authors upon reasonable request.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Data availability"}},{"value":"This work was funded by research grants from Diabetes UK (18\/0005805) and the Diabetes Research and Wellness Foundation (SCA\/PP\/12\/21). JB is supported by an independent fellowship funded by Research England\u2019s Expanding Excellence in England (E3) fund via EXCEED and the Helmsley Charitable Trust (2303-06709). PL and CM are supported by the RD Lawrence Fellowship from Diabetes UK (22\/0006378). In addition, this study was supported by the National Institute for Health and Care Research Exeter Biomedical Research Centre, Exeter. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. SJH was funded by the Professor David Matthews Non-Clinical Research Fellowship from the Diabetes Research and Wellness Foundation, and this work was supported on behalf of the Steve Morgan Foundation Type 1 Diabetes Grand Challenge by Breakthrough T1D UK, formerly JDRF, and the Steve Morgan Foundation (grant numbers 2-SRA-2024-1474-M-N and 2-SRA-2024-1473-M-N).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"FSW is a member of the editorial board of\n                      Diabetologia\n                      . The remaining authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Authors\u2019 relationships and activities"}},{"value":"FSW conceived the project and designed the experiments. EJR, WP, PL, SJH, JD, CM, SLW and JB contributed to experimental procedures and acquired and analysed the data. JB and FSW wrote the manuscript. JB, FSW and NGM contributed to interpreting the results and revised the manuscript. All authors reviewed and approved the manuscript. FSW is the guarantor of this work.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Contribution statement"}}]}}