6533b838fe1ef96bd12a3d5c
RESEARCH PRODUCT
IL‐10‐producing B cells are characterized by a specific methylation signature
Mario P. ColomboFrancesca MionCarlo PucilloSilvia TononHyun-dong ChangMatteo DugoJun DongMarco A. CassatellaGiuseppe PerruoloAndrea ZanelloAndreas RadbruchClaudio TripodoPatrizia ScapiniEmiliano Dallasubject
0301 basic medicineChronic lymphocytic leukemiaRegulatory B cellsImmunologyB-Lymphocyte SubsetsLymphoma Mantle-CellRegulatory Sequences Nucleic AcidBiologyLymphocyte ActivationB-cell malignanciesMice03 medical and health scienceschemistry.chemical_compoundInterleukin 100302 clinical medicineTranscription (biology)Immune ToleranceTumor MicroenvironmentmedicineAnimalsHumansImmunology and AllergyB cells; B-cell malignancies; DNA methylation; epigenetics; Interleukin 10; Immunology and Allergy; ImmunologyEpigeneticsB-Lymphocytes RegulatoryB cellsB cellDNA methylationepigeneticsGene Expression ProfilingB cells; B-cell malignancies; DNA methylation; epigenetics; Interleukin 10Cell DifferentiationMethylationmedicine.diseaseLeukemia Lymphocytic Chronic B-CellImmunity HumoralInterleukin-10Cell biologyMice Inbred C57BLInterleukin 10030104 developmental biologychemistryDNA methylationB-cell malignancieFemaleepigeneticDNA030215 immunologydescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2019-01-01 | European Journal of Immunology |