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.
| Original language | English |
|---|---|
| Pages (from-to) | 1213-1225 |
| Number of pages | 13 |
| Journal | European Journal of Immunology |
| Volume | 49 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Jan 1 2019 |
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Keywords
- B cells
- B-cell malignancies
- DNA methylation
- epigenetics
- Interleukin 10
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
Cite this
IL-10-producing B cells are characterized by a specific methylation signature. / Tonon, Silvia; Mion, Francesca; Dong, Jun; Chang, Hyun Dong; Dalla, Emiliano; Scapini, Patrizia; Perruolo, Giuseppe; Zanello, Andrea; Dugo, Matteo; Cassatella, Marco A.; Colombo, Mario P.; Radbruch, Andreas; Tripodo, Claudio; Pucillo, Carlo E.
In: European Journal of Immunology, Vol. 49, No. 8, 01.01.2019, p. 1213-1225.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - IL-10-producing B cells are characterized by a specific methylation signature
AU - Tonon, Silvia
AU - Mion, Francesca
AU - Dong, Jun
AU - Chang, Hyun Dong
AU - Dalla, Emiliano
AU - Scapini, Patrizia
AU - Perruolo, Giuseppe
AU - Zanello, Andrea
AU - Dugo, Matteo
AU - Cassatella, Marco A.
AU - Colombo, Mario P.
AU - Radbruch, Andreas
AU - Tripodo, Claudio
AU - Pucillo, Carlo E.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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.
AB - 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.
KW - B cells
KW - B-cell malignancies
KW - DNA methylation
KW - epigenetics
KW - Interleukin 10
UR - http://www.scopus.com/inward/record.url?scp=85065414938&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85065414938&partnerID=8YFLogxK
U2 - 10.1002/eji.201848025
DO - 10.1002/eji.201848025
M3 - Article
C2 - 31034584
AN - SCOPUS:85065414938
VL - 49
SP - 1213
EP - 1225
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 8
ER -