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浆细胞样树突状细胞和I型干扰素在抵抗自身胞外DNA中的功能
作者:小柯机器人 发布时间:2020/5/27 14:21:49

美国纽约大学Boris Reizis和法国波尔多大学Vanja Sisirak小组合作的最新研究发现,浆细胞样树突状细胞和I型干扰素促进细胞外B细胞对细胞外自身DNA的反应。2020年5月25日,《免疫》在线发表了这一成果。

研究人员发现Dnase1/3−/− 小鼠中抗DNA反应依赖于CD40L调控的T细胞而不依赖于生发中心的形成,该反应是通过定位于卵泡外区域的短时抗体形成细胞(AFC)进行的。I型干扰素(IFN-I)信号传导和产生IFN-I的浆细胞样树突状细胞(pDC)促进体内和体外DNA反应性AFC的分化,并且是自身免疫下游所必需的。

此外,细胞内DNA受体TLR9会在Dnase1/3−/− 小鼠中与另一种胞内核酸受体TLR7,冗余地促进抗双链DNA(dsDNA)反应和系统性红斑狼疮(SLE)样疾病。这些结果提示细胞外B细胞分化为短暂的AFCs,这些细胞是抗DNA自身反应的关键,并揭示了pDC、细胞内Toll样受体(TLRs)和IFN-I在该途径中的重要作用。

据悉,dsDNA的抗体类别转换在SLE中普遍存在并具有致病性,但对其产生机制的了解仍很少。缺少DNase DNASE1L3分泌的人和小鼠会快速产生抗dsDNA的抗体反应和SLE样疾病。

附:英文原文

Title: Plasmacytoid Dendritic Cells and Type I Interferon Promote Extrafollicular B Cell Responses to Extracellular Self-DNA

Author: Chetna Soni, Oriana A. Perez, William N. Voss, Joseph N. Pucella, Lee Serpas, Justin Mehl, Krystal L. Ching, Jule Goike, George Georgiou, Gregory C. Ippolito, Vanja Sisirak, Boris Reizis

Issue&Volume: 2020-05-25

Abstract: Class-switched antibodies to double-stranded DNA (dsDNA) are prevalent and pathogenicin systemic lupus erythematosus (SLE), yet mechanisms of their development remainpoorly understood. Humans and mice lacking secreted DNase DNASE1L3 develop rapid anti-dsDNAantibody responses and SLE-like disease. We report that anti-DNA responses in Dnase1l3/ mice require CD40L-mediated T cell help, but proceed independently of germinal centerformation via short-lived antibody-forming cells (AFCs) localized to extrafollicularregions. Type I interferon (IFN-I) signaling and IFN-I-producing plasmacytoid dendriticcells (pDCs) facilitate the differentiation of DNA-reactive AFCs in vivo and in vitro and are required for downstream manifestations of autoimmunity. Moreover, the endosomalDNA sensor TLR9 promotes anti-dsDNA responses and SLE-like disease in Dnase1l3/ mice redundantly with another nucleic acid-sensing receptor, TLR7. These resultsestablish extrafollicular B cell differentiation into short-lived AFCs as a key mechanismof anti-DNA autoreactivity and reveal a major contribution of pDCs, endosomal Toll-likereceptors (TLRs), and IFN-I to this pathway.

DOI: 10.1016/j.immuni.2020.04.015

Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30173-4

期刊信息

Immunity:《免疫》,创刊于1994年。隶属于细胞出版社,最新if:21.522
官方网址:https://www.cell.com/immunity/home
投稿链接:https://www.editorialmanager.com/immunity/default.aspx