A CD4+ T cell population expanded in lupus blood provides B cell help through interleukin-10 and succinate

被引：225

作者：

Caielli, Simone ^{[1
,2
,3
]}

Veiga, Diogo Troggian ^{[4
]}

Balasubramanian, Preetha ^{[2
,3
]}

Athale, Shruti ^{[1
]}

Domic, Bojana ^{[1
]}

Murat, Elise ^{[1
,2
,3
]}

Banchereau, Romain ^{[1
]}

Xu, Zhaohui ^{[1
]}

Chandra, Manjari ^{[1
]}

Chung, Cheng-Han ^{[4
]}

Walters, Lynnette ^{[1
,5
]}

Baisch, Jeanine ^{[1
,2
,3
]}

Wright, Tracey ^{[5
,6
]}

Punaro, Marilynn ^{[5
,6
]}

Nassi, Lorien ^{[5
,6
]}

Stewart, Katie ^{[5
,6
]}

Fuller, Julie ^{[5
,6
]}

Ucar, Duygu ^{[4
]}

Ueno, Hideki ^{[1
,7
]}

Zhou, Joseph ^{[8
]}

Banchereau, Jacques ^{[4
]}

Pascual, Virginia ^{[1
,2
,3
,5
]}

机构：

[1] Baylor Inst Immunol Res, Dallas, TX 75204 USA

[2] Weill Cornell Med, Drukier Inst Childrens Hlth, New York, NY 10065 USA

[3] Weill Cornell Med, Dept Pediat, New York, NY 10065 USA

[4] Jackson Lab Genom Med, Farmington, CT USA

[5] Texas Scottish Rite Hosp Children, Dallas, TX 75219 USA

[6] Univ Texas Southwestern Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA

[7] Mt Sinai Sch Med, New York, NY USA

[8] Pathol Biomed Labs, Lewisville, TX USA

来源：

NATURE MEDICINE | 2019年 / 25卷 / 01期

关键词：

PLASMACYTOID DENDRITIC CELLS; DISEASE-ACTIVITY; NUCLEIC-ACIDS; I INTERFERON; DIFFERENTIATION; CLASSIFICATION; MITOCHONDRIA; EXPRESSION; PROMOTE; ANTIGEN;

D O I：

10.1038/s41591-018-0254-9

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

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 (T-FH 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 centers(2). Here, we describe a CXCR5(-)CXCR3(+) programmed death 1 (PD1)(hi)CD4(+) helper T cell population distinct from T-FH 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 ligand(3). Targeting this pathway might blunt the initiation and/or perpetuation of extrafollicular humoral responses in SLE.

引用

页码：75 / +

页数：10

共 48 条

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Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells [J].