{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T11:44:07Z","timestamp":1790509447689,"version":"4.1.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T00:00:00Z","timestamp":1640044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Type 1 diabetes (T1D) is an autoimmune disease with a complex aetiology. B cells play an important role in the pathogenesis of T1D. Regulatory B cells (Bregs) are a subset of B cells that produce and secrete the inhibitory factor interleukin-10 (IL-10), thereby exerting an anti-inflammatory effect. It was recently discovered that T-cell immunoglobulin mucin domain 1 (Tim-1) is essential for maintaining Bregs function related to immune tolerance. However, the detailed understanding of Tim-1<jats:sup>+<\/jats:sup>Bregs and IL-10<jats:sup>+<\/jats:sup>Bregs in T1D patients is lacking. This study aimed to characterize the profile of B cell subsets in T1D patients compared with that in controls and determine whether Tim-1<jats:sup>+<\/jats:sup>Bregs and IL-10<jats:sup>+<\/jats:sup>Bregs play roles in T1D.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>A total of 47 patients with T1D, 30 patients with type 2 diabetes (T2D) and 24 healthy controls were recruited in this study. Flow cytometry was used to measure the levels of different B cell subsets (including B cells, plasmablasts, and Bregs) in the peripheral blood. Radiobinding assays were performed to detect the antibody titres of T1D patients. In addition, the correlations between different B cell subsets and patient parameters were investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with healthy controls, differences in frequency of Tim-1<jats:sup>+<\/jats:sup>Bregs were significantly decreased in patients with T1D (36.53 \u00b1 6.51<jats:italic>vs<\/jats:italic>. 42.25 \u00b1 6.83,<jats:italic>P<\/jats:italic>=0.02<jats:sup>*<\/jats:sup>), and frequency of IL-10<jats:sup>+<\/jats:sup>Bregs were lower than healthy controls (17.64 \u00b1 7.21<jats:italic>vs<\/jats:italic>. 24.52 \u00b1 11.69,<jats:italic>P<\/jats:italic>=0.009<jats:sup>**<\/jats:sup>), the frequency of total Bregs in PBMC was also decreased in patients with T1D (1.42 \u00b1 0.53<jats:italic>vs<\/jats:italic>. 1.99 \u00b1 0.93,<jats:italic>P<\/jats:italic>=0.002.<jats:sup>**<\/jats:sup>). We analyzed whether these alterations in B cells subsets were associated with clinical features. The frequencies of Tim-1<jats:sup>+<\/jats:sup>Bregs and IL-10<jats:sup>+<\/jats:sup>Bregs were negatively related to fasting blood glucose (FBG) (<jats:italic>r<\/jats:italic>=-0.25 and -0.22;<jats:italic>P<\/jats:italic>=0.01<jats:sup>*<\/jats:sup>and 0.03<jats:sup>*,<\/jats:sup>respectively). The frequencies of Tim-1<jats:sup>+<\/jats:sup>Bregs and IL-10<jats:sup>+<\/jats:sup>Bregs are positively correlated with fast C-peptide (FCP) (<jats:italic>r<\/jats:italic>=0.23 and 0.37;<jats:italic>P<\/jats:italic>=0.02<jats:sup>*<\/jats:sup>and 0.0001<jats:sup>***<\/jats:sup>, respectively). In addition, the frequency of IL-10<jats:sup>+<\/jats:sup>Breg was also negatively related to glycosylated haemoglobin (HbA1c) (<jats:italic>r<\/jats:italic>=-0.20,<jats:italic>P<\/jats:italic>=0.04<jats:sup>*<\/jats:sup>). The frequencies of Tim-1<jats:sup>+<\/jats:sup>Bregs, IL-10<jats:sup>+<\/jats:sup>Bregs and Bregs in T2D patients were reduced, but no statistically significant difference was found between other groups. Interestingly, there was positive correlation between the frequencies of Tim-1<jats:sup>+<\/jats:sup>Bregs and IL-10<jats:sup>+<\/jats:sup>Bregs in\u00a0T1D\u00a0(<jats:italic>r<\/jats:italic>=0.37,<jats:italic>P<\/jats:italic>=0.01<jats:sup>*<\/jats:sup>). Of note, it is worth noting that our study did not observe any correlations between B cell subsets and autoantibody titres.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study showed altered Tim-1 and IL-10 expression in regulatory B cell in T1D patients. Tim-1, as suggested by the present study, is associated with islet function and blood glucose levels. These findings indicate that Tim-1<jats:sup>+<\/jats:sup>Bregs and IL-10<jats:sup>+<\/jats:sup>Bregs were involved in the pathogenesis of T1D.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2021.773896","type":"journal-article","created":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T06:33:46Z","timestamp":1640068426000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Altered Tim-1 and IL-10 Expression in Regulatory B Cell Subsets in Type 1 Diabetes"],"prefix":"10.3389","volume":"12","author":[{"given":"Yikai","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiying","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junlin","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongzhi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiguang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,12,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1503\/cmaj.060244","article-title":"Type 1 Diabetes: Pathogenesis and Prevention","volume":"175","author":"Gillespie","year":"2006","journal-title":"CMAJ: Can Med Assoc J = J 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