IL-10-producing B cells are characterized by a specific methylation signature

Claudio Tripodo, Giuseppe Perruolo, Francesca Mion, Matteo Dugo, Silvia Tonon, Jun Dong, Andrea Zanello, Hyun-Dong Chang, Emiliano Dalla, Patrizia Scapini, Carlo E. Pucillo, Andreas Radbruch, Marco A. Cassatella, Mario P. Colombo

Risultato della ricerca: Articlepeer review

11 Citazioni (Scopus)

Abstract

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.
Lingua originaleEnglish
pagine (da-a)1213-1225
Numero di pagine13
RivistaEuropean Journal of Immunology
Volume49
Stato di pubblicazionePublished - 2019

All Science Journal Classification (ASJC) codes

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  • ???subjectarea.asjc.2400.2403???

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