Dataset Information

IL-10-Producing CD1d^hiCD5⁺ Regulatory B Cells May Play a Critical Role in Modulating Immune Homeostasis in Silicosis Patients.

ABSTRACT: Silicosis is characterized by chronic lung inflammation and fibrosis, which are extremely harmful to human health. The pathogenesis of silicosis involves uncontrolled immune processes. Evidence supports that regulatory B cells (Bregs) produce negative regulatory cytokines, such as IL-10, which can negatively regulate immune responses in inflammation and autoimmune diseases. Our previous study found that IL-10-producing B cells were involved in the development of silica-induced lung inflammation and fibrosis of mice. However, little is known about the role of Bregs in silicosis patients (SP). In this study, we found that serum concentrations of IL-10 were significantly increased in SP by using protein array screening. We further determined that the frequency of IL-10-producing CD1d^hiCD5⁺ Bregs, not IL-10-producing non-B lymphocytes, was significantly higher in SP compared to subjects under surveillance (SS) and healthy workers (HW) by flow cytometry. We also found that regulatory T cells (Tregs) and Th2 cytokines (IL-4, IL-5, and IL-13) were significantly increased in SP. Th1 cytokines (IFN-?, IL-2, and IL-12) and inflammatory cytokines (IL-1?, IL-6, and TNF-?) were not significantly different between SP, SS, and HW. Our study indicated that IL-10-producing CD1d^hiCD5⁺ Bregs might maintain Tregs and regulate Th1/Th2 polarization in SP, suggesting that IL-10-producing Bregs may play a critical role in modulating immune homeostasis in SP.

SUBMITTER: Chen Y

PROVIDER: S-EPMC5303715 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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IL-10-Producing CD1d<sup>hi</sup>CD5<sup>+</sup> Regulatory B Cells May Play a Critical Role in Modulating Immune Homeostasis in Silicosis Patients.

Chen Ying Y Li Chao C Lu Yiping Y Zhuang Huiying H Gu Weijia W Liu Bo B Liu Fangwei F Sun Jinkai J Yan Bo B Weng Dong D Chen Jie J

Frontiers in immunology 20170213

Silicosis is characterized by chronic lung inflammation and fibrosis, which are extremely harmful to human health. The pathogenesis of silicosis involves uncontrolled immune processes. Evidence supports that regulatory B cells (Bregs) produce negative regulatory cytokines, such as IL-10, which can negatively regulate immune responses in inflammation and autoimmune diseases. Our previous study found that IL-10-producing B cells were involved in the development of silica-induced lung inflammation ...[more]

PMID: 28243231

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Project description:Regulatory interleukin-10 (IL-10)-producing B cells (B10 cells) play a critical role in preventing and curing autoimmune diseases in experimental mouse models. However, the precise cellular and molecular mechanisms of action of B10 cells in humans, especially in patients with Crohn's disease (CD), remain to be determined. miR-155 regulates many physiological and pathological conditions, including inflammation such as that in CD. In this study, we aimed to explore the effect of miRNA-155 on IL-10 production by B cells in healthy controls (HCs) and CD patients. Interestingly, we found that CD24hiCD27+ B cells express high levels of miRNA-155 and IL-10, which are positively correlated. Additionally, CD24hiCD27+ B cells express higher levels of Toll-like receptor 9 than those found in other B cell subsets. Overexpression of miRNA-155 promotes IL-10 production, while inhibition of miRNA-155 decreases IL-10 production. We determined that miR-155 directly inhibits the expression of Jarid2, which reduces H3K27me3 binding to the IL10 promoter and increases IL-10 gene expression. In coculture systems, the CD24hiCD27+ B cells from HCs suppressed the secretion of TNFα and IFNγ by monocytes and T cells, respectively. However, the number and function of CD24hiCD27+ B cells from CD patients were decreased. Moreover, we found that miR-155 induces CD24hiCD27+ B cells to produce higher levels of TNFα instead of IL-10 in CD patients than in the controls and that the increased number of IL-10+TNFα+ B cells reduces the induction of Foxp3 expression and the inhibition of IFNγ production by CD4+CD25- T cells, as well as TNFα production by monocytes. Our study demonstrates the critical role of miRNA-155 in the regulation of IL-10 production by B cells and reveals the novel molecular mechanism underlying the functional impairment of B10 cells in CD patients. Our study has the potential to drive the development of B10 cell-based strategies to ameliorate disease progression in CD patients.

Dataset Information

IL-10-Producing CD1d^hiCD5⁺ Regulatory B Cells May Play a Critical Role in Modulating Immune Homeostasis in Silicosis Patients.

Publications

IL-10-Producing CD1d<sup>hi</sup>CD5<sup>+</sup> Regulatory B Cells May Play a Critical Role in Modulating Immune Homeostasis in Silicosis Patients.

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Dataset Information

IL-10-Producing CD1dhiCD5+ Regulatory B Cells May Play a Critical Role in Modulating Immune Homeostasis in Silicosis Patients.

Publications

IL-10-Producing CD1d<sup>hi</sup>CD5<sup>+</sup> Regulatory B Cells May Play a Critical Role in Modulating Immune Homeostasis in Silicosis Patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

IL-10-Producing CD1d^hiCD5⁺ Regulatory B Cells May Play a Critical Role in Modulating Immune Homeostasis in Silicosis Patients.