期刊
SCIENTIFIC REPORTS
卷 6, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/srep20044
关键词
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资金
- CONICYT Bicentennial Becas-Chile, Chile
- Wellcome Trust [097261/Z/11/Z]
- MRC [G0801537/ID: 88245]
- Medical Research Council (MRC) Centre for Transplantation, King's College London, UK - MRC [MR/J006742/1]
- Guy's and St Thomas' Charity [R080530, R090782]
- National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust
- King's College London
- European Union, Seventh Framework Programme [FP7] [HEALTH-F5-2010-260687]
- FP7-HEALTH-2012-INNOVATION-1 project [305147: BIO-DrIM]
- MRC [MR/L022699/1, G0801537] Funding Source: UKRI
- Wellcome Trust [097261/Z/11/Z] Funding Source: Wellcome Trust
- British Heart Foundation [RG/13/12/30395] Funding Source: researchfish
- Kidney Research UK [TF1/2014] Funding Source: researchfish
- Medical Research Council [G0801537, MR/J006742/1, MR/L022699/1] Funding Source: researchfish
A novel subset of human regulatory B-cells has recently been described. They arise from within the transitional B-cell subpopulation and are characterised by the production of IL-10. They appear to be of significant importance in regulating T-cell immunity in vivo. Despite this important function, the molecular mechanisms by which they control T-cell activation are incompletely defined. Here we show that transitional B-cells produced more IL-10 and expressed higher levels of IL-10 receptor after CD40 engagement compared to other B-cell subsets. Furthermore, under this stimulatory condition, CD86 expressed by transitional B-cells was down regulated and T-cell proliferation was reduced. We provide evidence to demonstrate that the down-regulation of CD86 expression by transitional B-cells was due to the autocrine effect of IL-10, which in turn leads to decreased T-cell proliferation and TNF-alpha production. This analysis was further extended to peripheral B-cells in kidney transplant recipients. We observed that B-cells from patients tolerant to the graft maintained higher IL-10 production after CD40 ligation, which correlates with lower CD86 expression compared to patients with chronic rejection. Hence, the results obtained in this study shed light on a new alternative mechanism by which transitional B-cells inhibit T-cell proliferation and cytokine production.
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