生发中心
免疫学
系统性红斑狼疮
生物
CXCR5型
狼疮性肾炎
自身抗体
白细胞介素21
医学
TLR7型
CD40
B细胞
T细胞
人口
免疫系统
Toll样受体
细胞毒性T细胞
抗体
体外
先天免疫系统
内科学
环境卫生
疾病
生物化学
作者
Simone Caielli,Diogo Troggian Veiga,Preetha Balasubramanian,Shruti Athale,Bojana Domic,Elise Murat,Romain Banchereau,Zhaohui Xu,Manjari Chandra,Cheng Han Chung,Lynnette Walters,Jeanine Baisch,Tracey Wright,Marilynn Punaro,Lorien Nassi,Katie Stewart,Julie Fuller,Duygu Ucar,Hideki Ueno,Joseph Zhou,Jacques Banchereau,Virginia Pascual
出处
期刊:Nature Medicine
[Springer Nature]
日期:2018-11-26
卷期号:25 (1): 75-81
被引量:174
标识
DOI:10.1038/s41591-018-0254-9
摘要
Understanding the mechanisms underlying autoantibody development will accelerate therapeutic target identification in autoimmune diseases such as systemic lupus erythematosus (SLE)1. Follicular helper T cells (TFH cells) have long been implicated in SLE pathogenesis. Yet a fraction of autoantibodies in individuals with SLE are unmutated, supporting that autoreactive B cells also differentiate outside germinal centers2. Here, we describe a CXCR5−CXCR3+ programmed death 1 (PD1)hiCD4+ helper T cell population distinct from TFH cells and expanded in both SLE blood and the tubulointerstitial areas of individuals with proliferative lupus nephritis. These cells produce interleukin-10 (IL-10) and accumulate mitochondrial reactive oxygen species as the result of reverse electron transport fueled by succinate. Furthermore, they provide B cell help, independently of IL-21, through IL-10 and succinate. Similar cells are generated in vitro upon priming naive CD4+ T cells with plasmacytoid dendritic cells activated with oxidized mitochondrial DNA, a distinct class of interferogenic toll-like receptor 9 ligand3. Targeting this pathway might blunt the initiation and/or perpetuation of extrafollicular humoral responses in SLE. A new population of T helper cells employs unique signals to support autoreactive B cells in patients with systemic lupus erythematosus.
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