• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

TRAF3-EWSR1 信号轴作为生发中心反应的检查点。

TRAF3-EWSR1 signaling axis acts as a checkpoint on germinal center responses.

机构信息

Department of Cell Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China.

Houston Methodist Cancer Center, Houston Methodist Research Institute, Houston Methodist Hospital , Houston, TX, USA.

出版信息

J Exp Med. 2023 Aug 7;220(8). doi: 10.1084/jem.20221483. Epub 2023 Apr 25.

DOI:10.1084/jem.20221483
PMID:37097293
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10130905/
Abstract

The formation of germinal centers (GCs) is crucial for humoral immunity and vaccine efficacy. Constant stimulation through microbiota drives the formation of constitutive GCs in Peyer's patches (PPs), which generate B cells that produce antibodies against gut antigens derived from commensal bacteria and infectious pathogens. However, the molecular mechanism that regulates this persistent process is poorly understood. We report that Ewing Sarcoma Breakpoint Region 1 (EWSR1) is a brake to constitutive GC generation and immunoglobulin G (IgG) production in PPs, vaccination-induced GC formation, and IgG responses. Mechanistically, EWSR1 suppresses Bcl6 upregulation after antigen encounter, thereby negatively regulating induced GC B cell generation and IgG production. We further showed that tumor necrosis factor receptor-associated factor (TRAF) 3 serves as a negative regulator of EWSR1. These results established that the TRAF3-EWSR1 signaling axis acts as a checkpoint for Bcl6 expression and GC responses, indicating that this axis is a therapeutic target to tune GC responses and humoral immunity in infectious diseases.

摘要

生发中心（GCs）的形成对于体液免疫和疫苗效力至关重要。通过微生物群的持续刺激，在派尔氏集合淋巴结（PPs）中形成组成性 GCs，这些 GCs 产生针对源自共生细菌和传染性病原体的肠道抗原的 B 细胞，从而产生抗体。然而，调节这一持续过程的分子机制尚未完全阐明。我们报告称，尤文肉瘤断点区域 1（EWSR1）是 PPs 中组成性 GC 生成和免疫球蛋白 G（IgG）产生、疫苗诱导的 GC 形成和 IgG 反应的制动因素。从机制上讲，EWSR1 抑制抗原作用后 Bcl6 的上调，从而负调控诱导的 GC B 细胞生成和 IgG 产生。我们进一步表明，肿瘤坏死因子受体相关因子（TRAF）3 是 EWSR1 的负调节剂。这些结果表明，TRAF3-EWSR1 信号轴作为 Bcl6 表达和 GC 反应的检查点，表明该轴是调节传染病中 GC 反应和体液免疫的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cc1/10130905/e3d1df4bbc3e/JEM_20221483_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cc1/10130905/303c9566cc9b/JEM_20221483_GA.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cc1/10130905/d63a8d8048af/JEM_20221483_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cc1/10130905/f409092b5588/JEM_20221483_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cc1/10130905/5134c928cc95/JEM_20221483_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cc1/10130905/9f433ca60af9/JEM_20221483_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cc1/10130905/b91af14f2857/JEM_20221483_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cc1/10130905/ae7104f25148/JEM_20221483_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cc1/10130905/3af7b84be4de/JEM_20221483_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cc1/10130905/7cd75dfdaf8f/JEM_20221483_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cc1/10130905/602bdf0240dd/JEM_20221483_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cc1/10130905/2a25170edae3/JEM_20221483_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cc1/10130905/cba497fcf427/JEM_20221483_FigS5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cc1/10130905/e3d1df4bbc3e/JEM_20221483_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cc1/10130905/303c9566cc9b/JEM_20221483_GA.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cc1/10130905/d63a8d8048af/JEM_20221483_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cc1/10130905/f409092b5588/JEM_20221483_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cc1/10130905/5134c928cc95/JEM_20221483_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cc1/10130905/9f433ca60af9/JEM_20221483_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cc1/10130905/b91af14f2857/JEM_20221483_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cc1/10130905/ae7104f25148/JEM_20221483_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cc1/10130905/3af7b84be4de/JEM_20221483_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cc1/10130905/7cd75dfdaf8f/JEM_20221483_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cc1/10130905/602bdf0240dd/JEM_20221483_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cc1/10130905/2a25170edae3/JEM_20221483_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cc1/10130905/cba497fcf427/JEM_20221483_FigS5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cc1/10130905/e3d1df4bbc3e/JEM_20221483_Fig7.jpg

相似文献

1
TRAF3-EWSR1 signaling axis acts as a checkpoint on germinal center responses.TRAF3-EWSR1 信号轴作为生发中心反应的检查点。
J Exp Med. 2023 Aug 7;220(8). doi: 10.1084/jem.20221483. Epub 2023 Apr 25.
2
Antigen receptor signaling and cell death resistance controls intestinal humoral response zonation.抗原受体信号和细胞死亡抵抗控制肠道体液反应分区。
Immunity. 2023 Oct 10;56(10):2373-2387.e8. doi: 10.1016/j.immuni.2023.08.018. Epub 2023 Sep 14.
3
Affinity-based clonal selection in Peyer's patches.派尔集合淋巴结中的基于亲和力的克隆选择。
Curr Opin Immunol. 2022 Feb;74:100-105. doi: 10.1016/j.coi.2021.11.002. Epub 2021 Nov 27.
4
B Cell Diversification Is Uncoupled from SAP-Mediated Selection Forces in Chronic Germinal Centers within Peyer's Patches.B 细胞多样化与 Peyer 斑内慢性生发中心中 SAP 介导的选择力无关。
Cell Rep. 2020 Feb 11;30(6):1910-1922.e5. doi: 10.1016/j.celrep.2020.01.032.
5
Dietary Antigens Induce Germinal Center Responses in Peyer's Patches and Antigen-Specific IgA Production.饮食抗原在派伊尔斑诱导生发中心反应和抗原特异性 IgA 产生。
Front Immunol. 2019 Oct 15;10:2432. doi: 10.3389/fimmu.2019.02432. eCollection 2019.
6
BCR affinity differentially regulates colonization of the subepithelial dome and infiltration into germinal centers within Peyer's patches.BCR 亲和力差异调节派伊尔氏结黏膜下穹窿的定植和生发中心的浸润。
Nat Immunol. 2019 Apr;20(4):482-492. doi: 10.1038/s41590-019-0325-1. Epub 2019 Mar 4.
7
Cecal Patches Generate Abundant IgG2b-Bearing B Cells That Are Reactive to Commensal Microbiota.盲肠结集结大量可反应共生微生物群的 IgG2b 抗体生成 B 细胞。
J Immunol Res. 2022 May 4;2022:3974141. doi: 10.1155/2022/3974141. eCollection 2022.
8
Re-utilization of germinal centers in multiple Peyer's patches results in highly synchronized, oligoclonal, and affinity-matured gut IgA responses.生发中心在多个派伊尔氏结中的再利用导致高度同步、寡克隆和亲和力成熟的肠道 IgA 应答。
Mucosal Immunol. 2013 Jan;6(1):122-35. doi: 10.1038/mi.2012.56. Epub 2012 Jul 11.
9
Surface phenotype of Peyer's patch germinal center cells: implications for the role of germinal centers in B cell differentiation.派尔集合淋巴结生发中心细胞的表面表型：对生发中心在B细胞分化中作用的启示
J Immunol. 1982 Dec;129(6):2698-707.
10
Integrin CD11b provides a new marker of pre-germinal center IgA+ B cells in murine Peyer's patches.整合素 CD11b 为肠道派尔集合淋巴结生发中心前 IgA+B 细胞提供了一个新的标志物。
Int Immunol. 2022 Apr 20;34(5):249-262. doi: 10.1093/intimm/dxab113.

引用本文的文献

1
PGRN Inhibits Early B-cell Activation and IgE Production Through the IFITM3-STAT1 Signaling Pathway in Asthma.颗粒蛋白前体通过哮喘中IFITM3-STAT1信号通路抑制早期B细胞活化和IgE产生。
Adv Sci (Weinh). 2024 Dec;11(45):e2403939. doi: 10.1002/advs.202403939. Epub 2024 Oct 16.

本文引用的文献

1
Germinal Centers.生发中心。
Annu Rev Immunol. 2022 Apr 26;40:413-442. doi: 10.1146/annurev-immunol-120419-022408. Epub 2022 Feb 3.
2
The unique biology of germinal center B cells.生发中心 B 细胞的独特生物学特性。
Immunity. 2021 Aug 10;54(8):1652-1664. doi: 10.1016/j.immuni.2021.07.015.
3
DYRK1a mediates BAFF-induced noncanonical NF-κB activation to promote autoimmunity and B-cell leukemogenesis.DYRK1a 介导 BAFF 诱导的非经典 NF-κB 激活，促进自身免疫和 B 细胞白血病发生。
Blood. 2021 Dec 9;138(23):2360-2371. doi: 10.1182/blood.2021011247.
4
SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses.SARS-CoV-2 mRNA 疫苗可诱导持久的人体生发中心反应。
Nature. 2021 Aug;596(7870):109-113. doi: 10.1038/s41586-021-03738-2. Epub 2021 Jun 28.
5
Dynamic regulation of B cell complement signaling is integral to germinal center responses.B 细胞补体信号的动态调控是生发中心反应的重要组成部分。
Nat Immunol. 2021 Jun;22(6):757-768. doi: 10.1038/s41590-021-00926-0. Epub 2021 May 24.
6
The Amount of BCL6 in B Cells Shortly after Antigen Engagement Determines Their Representation in Subsequent Germinal Centers.抗原结合后不久 B 细胞中 BCL6 的量决定了它们在随后生发中心中的表现。
Cell Rep. 2020 Feb 4;30(5):1530-1541.e4. doi: 10.1016/j.celrep.2020.01.009.
7
Preventing abnormal NF-κB activation and autoimmunity by Otub1-mediated p100 stabilization.通过 Otub1 介导的 p100 稳定来防止异常 NF-κB 激活和自身免疫。
Cell Res. 2019 Jun;29(6):474-485. doi: 10.1038/s41422-019-0174-3. Epub 2019 May 13.
8
B Cell Responses: Cell Interaction Dynamics and Decisions.B 细胞反应：细胞相互作用动力学与决策。
Cell. 2019 Apr 18;177(3):524-540. doi: 10.1016/j.cell.2019.03.016.
9
Maternal Immunization Confers Protection to the Offspring against an Attaching and Effacing Pathogen through Delivery of IgG in Breast Milk.母体免疫通过在母乳中传递 IgG 为后代提供针对附着和消除病原体的保护。
Cell Host Microbe. 2019 Feb 13;25(2):313-323.e4. doi: 10.1016/j.chom.2018.12.015. Epub 2019 Jan 24.
10
EWSR1, a multifunctional protein, regulates cellular function and aging via genetic and epigenetic pathways.EWSR1 是一种多功能蛋白，通过遗传和表观遗传途径调节细胞功能和衰老。
Biochim Biophys Acta Mol Basis Dis. 2019 Jul 1;1865(7):1938-1945. doi: 10.1016/j.bbadis.2018.10.042. Epub 2018 Nov 24.