期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 49, 期 8, 页码 1213-1225出版社
WILEY
DOI: 10.1002/eji.201848025
关键词
B cells; B-cell malignancies; DNA methylation; epigenetics; Interleukin 10
类别
资金
- Associazione Italiana Ricerca sul Cancro (AIRC) [18425, 15561]
- Progetti di Ricerca di Interesse Nazionale (PRIN) [2015YYKPNN_003, 20174T7NXL 004]
- AIRC [20339]
- PRIN [2015YYKPNN_002]
- German Research Council (DFG) [CRC Transregio 130]
Among the family of regulatory B cells, the subset able to produce interleukin-10 (IL-10) is the most studied, yet its biology is still a matter of investigation. The DNA methylation profiling of the il-10 gene locus revealed a novel epigenetic signature characterizing murine B cells ready to respond through IL-10 synthesis: a demethylated region located 4.5 kb from the transcription starting site (TSS), that we named early IL10 regulatory region (eIL10rr). This feature allows to distinguish B cells that are immediately prone and developmentally committed to IL-10 production from those that require a persistent stimulation to exert an IL-10-mediated regulatory function. These late IL-10 producers are instead characterized by a delayed IL10 regulatory region (dIL10rr), a partially demethylated DNA portion located 9 kb upstream from the TSS. A demethylated region was also found in human IL-10-producing B cells and, very interestingly, in some B-cell malignancies, such as chronic lymphocytic leukemia and mantle cell lymphoma, characterized by an immunosuppressive microenvironment. Our findings define murine and human regulatory B cells as an epigenetically controlled functional state of mature B cell subsets and open a new perspective on IL-10 regulation in B cells in homeostasis and disease.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据