miR-155 Regulates IL-10-Producing CD24(hi)CD27(+) B Cells and Impairs Their Function in Patients with Crohn's Disease.
miR-155 Regulates IL-10-Producing CD24(hi)CD27(+) B Cells and Impairs Their Function in Patients with Crohn's Disease.
复制标题
mir-155 调节克罗恩病患者产生 IL-10 的 CD24(hi)CD27( ) B 细胞并损害其功能
DOI：
10.3389/fimmu.2017.00914
复制
发表时间：
2017
影响因子：
7.3
通讯作者：
Shen L
中科院分区：
文献类型：
--
作者：
Zheng Y;Ge W;Ma Y;Xie G;Wang W;Han L;Bian B;Li L;Shen L
调节性白介素10(IL-10)产生的B细胞(B10细胞)在预防和治疗实验性小鼠自身免疫性疾病中起着关键作用。然而，B10细胞在人类，特别是在克罗恩病(CD)患者中的确切细胞和分子作用机制仍有待确定。MIR-155调节许多生理和病理条件，包括CD中的炎症。本研究旨在探讨miRNA-155对正常人和CD患者B细胞产生IL-10的影响。有趣的是，我们发现CD24hiCD27+B细胞高水平表达miRNA-155和IL-10，两者呈正相关。此外，CD24hiCD27+B细胞比其他B细胞亚群表达更高水平的Toll样受体9。MiRNA-155的过表达促进IL-10的产生，而抑制miRNA-155则减少IL-10的产生。我们确定miR-155直接抑制Jarid2的表达，从而减少H3K27me3与IL10启动子的结合，并增加IL-10基因的表达。在共培养体系中，CD24hiCD27+B细胞可抑制单核细胞分泌肿瘤坏死因子α，抑制T细胞分泌干扰素γ。CD患者外周血中CD24hiCD27+B细胞数量和功能均下降。此外，我们还发现，在CD患者中，miR155诱导CD24hiCD27+B细胞产生较高水平的肿瘤坏死因子α而不是IL-10。IL-10+肿瘤坏死因子α+B细胞数量的增加减少了CD+CD25γT细胞对Foxp3表达的诱导和对干扰素−的抑制，以及单核细胞产生肿瘤坏死因子α。我们的研究证实了miRNA-155在调节B细胞产生IL-10中的关键作用，并揭示了CD患者B10细胞功能损害的新的分子机制。我们的研究有可能推动基于B10细胞的策略的发展，以改善CD患者的疾病进展。
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.
登录
查看更多内容
影响因子：
8.6
作者：
Banko, Zsuzsanna;Pozsgay, Judit;Sarmay, Gabriella
通讯作者：
Sarmay, Gabriella
影响因子：
12.8
作者：
Pathak, Surajit;Grillo, Alessia Rosaria;Scarpa, Melania;Brun, Paola;D'Inca, Renata;Nai, Laura;Banerjee, Antara;Cavallo, Donatella;Barzon, Luisa;Palu, Giorgio;Sturniolo, Giacomo Carlo;Buda, Andrea;Castagliuolo, Ignazio
通讯作者：
Castagliuolo, Ignazio
DOI：
10.4049/jimmunol.1300649
发表时间：
2013-09-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Maseda D;Candando KM;Smith SH;Kalampokis I;Weaver CT;Plevy SE;Poe JC;Tedder TF
通讯作者：
Tedder TF
影响因子：
32.4
作者：
O'Connell RM;Kahn D;Gibson WS;Round JL;Scholz RL;Chaudhuri AA;Kahn ME;Rao DS;Baltimore D
通讯作者：
Baltimore D
影响因子：
29.4
作者：
Atreya, Raja;Zimmer, Michael;Neurath, Markus F.
通讯作者：
Neurath, Markus F.