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We have completed a clinical trial in renal transplant patients in which the significant biological effect was the increase of B cells with a regulatory phenotype in the blood of kidney transplant patients. The mechanisms by which Tregs regulate B cells and the specific molecules involved in this process remained poorly understood. In this study, we employed an in vitro system of co-culture of peripherally purified B cells and expanded Tregs to show that Tregs can induce a population of memory B cells that express IL-10 and CD25. This subset of B cells has been previously identified as one of humans\u2019 regulatory B cell populations. Notably, these expanded Tregs\u2019 regulation of B cells was found to be independent of IL-10 and reliant on direct cell contact. We established that TIM3 expression by Tregs was crucial for the induction of IL-10-producing CD25\n                      <jats:sup>+<\/jats:sup>\n                      memory B cells. Our findings suggest that TIM3 is a critical molecule for the induction of regulatory B cells by Tregs, indicating that TIM3 expression by adoptively transferred Tregs is vital in diseases where B cells play a pathogenic role.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Messages<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Expanded Tregs induce IL-10+ CD25+ B cells.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>TIM3 expression on Tregs is crucial for IL-10+ B cell induction.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Tregs require direct cell contact to regulate B cells.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Blocking TIM3 reduces IL-10+ B cells but increases IFN-\u03b3, TNF-\u03b1, IL-17.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Tregs enhance regulatory B cell differentiation, promoting tolerance.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00109-025-02606-0","type":"journal-article","created":{"date-parts":[[2025,12,27]],"date-time":"2025-12-27T02:24:02Z","timestamp":1766802242000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["TIM3-mediated differentiation of IL-10-producing CD25+\u2009B cells by expanded regulatory T cells"],"prefix":"10.1007","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7135-9967","authenticated-orcid":false,"given":"Rowa Y.","family":"Alhabbab","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7922-7499","authenticated-orcid":false,"given":"Daniela","family":"Mastronicola","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4496-3215","authenticated-orcid":false,"given":"Giovanna","family":"Lombardi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3942-5201","authenticated-orcid":false,"given":"Cristiano","family":"Scott\u00e0","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,12,27]]},"reference":[{"issue":"11","key":"2606_CR1","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1093\/intimm\/dxz043","volume":"31","author":"T Yamaguchi","year":"2019","unstructured":"Yamaguchi T et al (2019) Theoretical modeling reveals that regulatory T cells increase T-cell interaction with antigen-presenting cells for stable immune tolerance. 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