Human PD-1(hi)CD8(+) T Cells Are a Cellular Source of IL-21 in Rheumatoid Arthritis.
Human PD-1(hi)CD8(+) T Cells Are a Cellular Source of IL-21 in Rheumatoid Arthritis.
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DOI：
10.3389/fimmu.2021.654623
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发表时间：
2021
影响因子：
7.3
通讯作者：
Niiro H
中科院分区：
文献类型：
--
作者：
Higashioka K;Yoshimura M;Sakuragi T;Ayano M;Kimoto Y;Mitoma H;Ono N;Arinobu Y;Kikukawa M;Yamada H;Horiuchi T;Akashi K;Niiro H
类风湿性关节炎（RA）是一种典型的自身抗体驱动的自身免疫性疾病，其中T-B相互作用起着关键作用。最近的综合分析表明，PD-1+ CD 8 + T细胞以及两种不同的产生IL-21的PD-1+ CD 4 + T细胞亚群，滤泡辅助T（Tfh）和外周辅助T（Tph）细胞，参与RA的发病机制。在此，我们的目的是澄清产生IL-21的CD 8 + T细胞在人类中的产生机制，并在RA患者中描述这种新的亚群。对健康对照组（HC）和RA患者外周血（PB）和关节液（SF）中的CD 8 + T细胞进行IL-21 mRNA和蛋白的检测。我们评估了HCPB、RAPB和RASF中产生IL-21的CD 8 + T细胞的表面标志物、细胞因子和转录谱。产生IL-21的CD 8 + T细胞在CD 45 RA-（记忆）PD-1+，特别是PD-1hi亚群中富集，IL-12和IL-21协同诱导幼稚CD 8 + T细胞产生IL-21。HCPB中的记忆PD-1hiCD 8 + T细胞以IL-21依赖性方式促进浆母细胞分化和IgG产生。此外，RASF和RAPB中的PD-1hiCD 8 + T细胞产生大量IL-21，其特征在于高水平的CD 28、ICOS、CD 69、HLA-DR和CCR 2，但不包括CXCR 5。此外，PD-1hiCD 8 + T细胞表达高水平的MAF和PRDM 1转录物，这是在Tph细胞中观察到的特征。产生IL-21的PD-1 hiCD 8 + T细胞的鉴定扩展了我们对RA中具有B辅助功能的T细胞亚群的了解。选择性靶向这些亚群可以为开发这种疾病的新治疗策略铺平道路。
Rheumatoid arthritis (RA) is a prototypical autoantibody-driven autoimmune disease in which T-B interactions play a critical role. Recent comprehensive analysis suggests that PD-1+CD8+ T cells as well as two distinct IL-21-producing PD-1+CD4+ T cell subsets, follicular helper T (Tfh) and peripheral helper T (Tph) cells, are involved in the pathogenesis of RA. Herein, we aimed to clarify a generation mechanism of IL-21-producing CD8+ T cells in humans, and to characterize this novel subset in patients with RA. CD8+ T cells in the peripheral blood (PB) and synovial fluid (SF) of healthy control (HC) and patients with RA were subject to the analysis of IL-21 mRNA and protein. We evaluated the surface marker, cytokine and transcription profiles of IL-21-producing CD8+ T cells in HCPB, RAPB and RASF. IL-21-producing CD8+ T cells were enriched in the CD45RA-(memory) PD-1+, especially PD-1hi subpopulation, and IL-12 and IL-21 synergistically induced IL-21 production by naïve CD8+ T cells. Memory PD-1hiCD8+ T cells in HCPB facilitated plasmablast differentiation and IgG production in an IL-21-dependent manner. In addition, PD-1hiCD8+ T cells in RASF and RAPB produced large amounts of IL-21 and were characterized by high levels of CD28, ICOS, CD69, HLA-DR, and CCR2 but not CXCR5. Furthermore, PD-1hiCD8+ T cells expressed high levels of transcripts of MAF and PRDM1, a feature observed in Tph cells. Identification of IL-21-producing PD-1hiCD8+ T cells expands our knowledge of T cell subsets with B helper functions in RA. Selective targeting of these subsets could pave an avenue for the development of novel treatment strategies for this disease.
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DOI：
10.1084/jem.20130323
发表时间：
2013-11-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Deenick EK;Avery DT;Chan A;Berglund LJ;Ives ML;Moens L;Stoddard JL;Bustamante J;Boisson-Dupuis S;Tsumura M;Kobayashi M;Arkwright PD;Averbuch D;Engelhard D;Roesler J;Peake J;Wong M;Adelstein S;Choo S;Smart JM;French MA;Fulcher DA;Cook MC;Picard C;Durandy A;Klein C;Holland SM;Uzel G;Casanova JL;Ma CS;Tangye SG
通讯作者：
Tangye SG
影响因子：
7.5
作者：
Le, Kieu-Suong;Ame-Thomas, Patricia;Olive, Daniel
通讯作者：
Olive, Daniel
影响因子：
13.3
作者：
Liu, Chen;Wang, Dongwei;Wang, Hui
通讯作者：
Wang, Hui
DOI：
10.4049/jimmunol.1201678
发表时间：
2013-02-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Ding BB;Bi E;Chen H;Yu JJ;Ye BH
通讯作者：
Ye BH
DOI：
10.1084/jem.20011565
发表时间：
2002-05-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kang YM;Zhang X;Wagner UG;Yang H;Beckenbaugh RD;Kurtin PJ;Goronzy JJ;Weyand CM
通讯作者：
Weyand CM