Recent Advances in Lupus B Cell Biology: PI3K, IFNγ, and Chromatin.
Recent Advances in Lupus B Cell Biology: PI3K, IFNγ, and Chromatin.
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DOI：
10.3389/fimmu.2020.615673
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发表时间：
2020
影响因子：
7.3
通讯作者：
Satterthwaite AB
中科院分区：
文献类型：
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作者：
Bacalao MA;Satterthwaite AB
在自身免疫性疾病系统性红斑狼疮 (SLE) 中，会形成自身抗体，促进炎症和组织损伤。人们对了解 SLE 发病机制中涉及的 B 细胞紊乱产生了浓厚的兴趣。过去几年在三个领域取得了特别丰硕的成果：PI3K 信号传导在 B 细胞耐受性丧失中的作用、IFNγ 信号传导在自身免疫发展中的作用以及 SLE B 细胞染色质可及性变化的表征。 PI3K 通路协调参与 B 细胞发育和激活的各种下游信号分子。它由磷酸酶 PTEN 和 SHIP-1 控制。 B 细胞中缺乏这些磷酸酶中的任何一种的小鼠模型都会出现自身免疫性疾病，并表现出 B 细胞耐受性缺陷。对人类 SLE B 细胞的有限研究表明，某些患者中 PTEN 表达减少或 PI3K 下游信号事件增加。长期以来，人们都知道 IFNγ 在 SLE 患者和狼疮小鼠模型中都会升高。新数据表明，小鼠狼疮中的自身反应性生发中心 (GC) 和自身抗体的形成需要 B 细胞上的 IFNγR 表达。此外，IFNγ促进B细胞中BCL6、IL-6和T-bet的转录增加，这也促进GC和自身抗体的形成。 IFNγ 还会诱导人类 B 细胞的表观遗传变化。 SLE B 细胞表现出显着的表观遗传重编程，包括参与 B 细胞激活和浆细胞 (PC) 分化的转录因子基序染色质可及性增强，以及 DNA 甲基化和组蛋白修饰的改变。组蛋白脱乙酰酶抑制剂至少部分通过其阻止 B 细胞类别转换和分化为浆细胞的能力来限制小鼠狼疮模型中的疾病发展。本综述将讨论过去几年与 SLE B 细胞生物学这些领域相关的相关发现。
In the autoimmune disease Systemic Lupus Erythematosus (SLE), autoantibodies are formed that promote inflammation and tissue damage. There has been significant interest in understanding the B cell derangements involved in SLE pathogenesis. The past few years have been particularly fruitful in three domains: the role of PI3K signaling in loss of B cell tolerance, the role of IFNγ signaling in the development of autoimmunity, and the characterization of changes in chromatin accessibility in SLE B cells. The PI3K pathway coordinates various downstream signaling molecules involved in B cell development and activation. It is governed by the phosphatases PTEN and SHIP-1. Murine models lacking either of these phosphatases in B cells develop autoimmune disease and exhibit defects in B cell tolerance. Limited studies of human SLE B cells demonstrate reduced expression of PTEN or increased signaling events downstream of PI3K in some patients. IFNγ has long been known to be elevated in both SLE patients and mouse models of lupus. New data suggests that IFNγR expression on B cells is required to develop autoreactive germinal centers (GC) and autoantibodies in murine lupus. Furthermore, IFNγ promotes increased transcription of BCL6, IL-6 and T-bet in B cells, which also promote GC and autoantibody formation. IFNγ also induces epigenetic changes in human B cells. SLE B cells demonstrate significant epigenetic reprogramming, including enhanced chromatin accessibility at transcription factor motifs involved in B cell activation and plasma cell (PC) differentiation as well as alterations in DNA methylation and histone modifications. Histone deacetylase inhibitors limit disease development in murine lupus models, at least in part via their ability to prevent B cell class switching and differentiation into plasma cells. This review will discuss relevant discoveries of the past several years pertaining to these areas of SLE B cell biology.
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DOI：
10.1002/art.39856
发表时间：
2017-02
期刊：
Arthritis & rheumatology (Hoboken, N.J.)
影响因子：
--
作者：
Clowse ME;Wallace DJ;Furie RA;Petri MA;Pike MC;Leszczyński P;Neuwelt CM;Hobbs K;Keiserman M;Duca L;Kalunian KC;Galateanu C;Bongardt S;Stach C;Beaudot C;Kilgallen B;Gordon C;EMBODY Investigator Group
通讯作者：
EMBODY Investigator Group
影响因子：
4.4
作者：
Chodisetti, Sathi Babu;Fike, Adam J.;Rahman, Ziaur S. M.
通讯作者：
Rahman, Ziaur S. M.
影响因子：
2.3
作者：
Aihara, Y;Mori, M;Yokota, S
通讯作者：
Yokota, S
影响因子：
4.4
作者：
Chen, Yingjia;Hu, Fanlei;Liu, Wanli
通讯作者：
Liu, Wanli
DOI：
10.4049/jimmunol.2000170
发表时间：
2020-05-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
通讯作者：
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