{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:30:51Z","timestamp":1792099851635,"version":"4.4.0"},"reference-count":28,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2019,5,7]],"date-time":"2019-05-07T00:00:00Z","timestamp":1557187200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["18425"],"award-info":[{"award-number":["18425"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Among the family of regulatory B\u00a0cells, the subset able to produce interleukin\u201010 (IL\u201010) is the most studied, yet its biology is still a matter of investigation. The DNA methylation profiling of the\n                    <jats:italic>il\u201010<\/jats:italic>\n                    gene\n                    <jats:italic>locus<\/jats:italic>\n                    revealed a novel epigenetic signature characterizing murine B\u00a0cells ready to respond through IL\u201010 synthesis: a demethylated region located 4.5 kb from the transcription starting site (TSS), that we named\n                    <jats:italic>early IL10 regulatory region<\/jats:italic>\n                    (eIL10rr). This feature allows to distinguish B\u00a0cells that are immediately prone and developmentally committed to IL\u201010 production from those that require a persistent stimulation to exert an IL\u201010\u2010mediated regulatory function. These late IL\u201010 producers are instead characterized by a\n                    <jats:italic>delayed IL10 regulatory region<\/jats:italic>\n                    (dIL10rr), a partially demethylated DNA portion located 9 kb upstream from the TSS. A demethylated region was also found in human IL\u201010\u2010producing B\u00a0cells and, very interestingly, in some B\u2010cell malignancies, such as chronic lymphocytic leukemia and mantle cell lymphoma, characterized by an immunosuppressive microenvironment. Our findings define murine and human regulatory B\u00a0cells as an epigenetically controlled functional state of mature B\u00a0cell subsets and open a new perspective on IL\u201010 regulation in B\u00a0cells in homeostasis and disease.\n                  <\/jats:p>","DOI":"10.1002\/eji.201848025","type":"journal-article","created":{"date-parts":[[2019,4,30]],"date-time":"2019-04-30T21:11:19Z","timestamp":1556658679000},"page":"1213-1225","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["IL\u201010\u2010producing B\u00a0cells are characterized by a specific methylation signature"],"prefix":"10.1002","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3361-2906","authenticated-orcid":false,"given":"Silvia","family":"Tonon","sequence":"first","affiliation":[{"name":"Department of Medical Area University of Udine  Udine 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