Increased Development of Th1, Th17, and Th1.17 Cells Under T1 Polarizing Conditions in Juvenile Idiopathic Arthritis.
Increased Development of Th1, Th17, and Th1.17 Cells Under T1 Polarizing Conditions in Juvenile Idiopathic Arthritis.
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DOI：
10.3389/fimmu.2022.848168
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发表时间：
2022
影响因子：
7.3
通讯作者：
Aune, Thomas M.
中科院分区：
文献类型：
--
作者：
Patrick, Anna E.;Shoaff, Kayla;Esmond, Tashawna;Patrick, David M.;Flaherty, David K.;Graham, T. Brent;Crooke, Philip S.;Thompson, Susan;Aune, Thomas M.
关键词：
在幼年特发性关节炎 (JIA) 中，炎症 T 细胞及其产生的细胞因子是药物靶标，并在疾病发病机制中发挥作用。尽管其临床重要性，但所涉及的炎症 T 细胞的来源和类型仍不清楚。 T 细胞对极化因子作出反应，启动多种免疫类型来对抗感染，包括免疫类型 1 (T1)、2 (T2) 和 3 (T17)。极化因子驱动 CD4+ T 细胞向 T 辅助 (Th) 细胞亚型发展，CD8+ T 细胞向细胞毒性 T 细胞 (Tc) 亚型发展。 T1 和 T17 极化分别与自身免疫和细胞因子 IFNγ 和 IL-17 的产生相关。我们发现，JIA 和儿童健康对照 (HC) 外周血单核细胞非常相似，在 T1、T2 和 T17 极化时，CD4+ 和 CD8+ 幼稚 T 细胞亚群、记忆 T 细胞亚群、T 细胞增殖以及 CD4+ 和 CD8+ T 细胞亚群的频率相同。然而，在 T1 极化条件下，JIA 细胞产生增加的 IFNγ 并不适当地产生 IL-17。在 T17 极化条件下，JIA T 细胞产生的 IL-17 增加。通过定量 PCR 和 RNA 测序检测 IFNγ、IL-17、Tbet 和 RORγT 的基因表达，揭示了 JIA 极化 T1 细胞中免疫反应的激活和 IL-17 信号通路的不当激活。极化的JIA T1细胞由Th和Tc细胞组成，其中Th细胞产生IFNγ（Th1）、IL-17（Th17），并且IFNγ-IL-17（Th1.17）和Tc细胞都产生IFNγ（Tc1）。 JIA 极化的 CD4+ T1 细胞表达 Tbet 和 RORγT，转录因子的较高表达与 IL-17 产生细胞的较高频率相关。来自 JIA 的 T1 极化幼稚 CD4+ 细胞也比 HC 产生更多的 IFNγ 和 IL-17。我们发现，在 JIA 中，T1 极化不适当地产生 Th1、Th17 和 Th1.17 细胞。我们的数据提供了一种工具，用于研究 JIA 中异质炎症 T 细胞在 T1 极化条件下的发育，并用于识别作为药物靶点和诊断标记物的重要致病性免疫细胞。
In juvenile idiopathic arthritis (JIA) inflammatory T cells and their produced cytokines are drug targets and play a role in disease pathogenesis. Despite their clinical importance, the sources and types of inflammatory T cells involved remain unclear. T cells respond to polarizing factors to initiate types of immunity to fight infections, which include immunity types 1 (T1), 2 (T2), and 3 (T17). Polarizing factors drive CD4+ T cells towards T helper (Th) cell subtypes and CD8+ T cells towards cytotoxic T cell (Tc) subtypes. T1 and T17 polarization are associated with autoimmunity and production of the cytokines IFNγ and IL-17 respectively. We show that JIA and child healthy control (HC) peripheral blood mononuclear cells are remarkably similar, with the same frequencies of CD4+ and CD8+ naïve and memory T cell subsets, T cell proliferation, and CD4+ and CD8+ T cell subsets upon T1, T2, and T17 polarization. Yet, under T1 polarizing conditions JIA cells produced increased IFNγ and inappropriately produced IL-17. Under T17 polarizing conditions JIA T cells produced increased IL-17. Gene expression of IFNγ, IL-17, Tbet, and RORγT by quantitative PCR and RNA sequencing revealed activation of immune responses and inappropriate activation of IL-17 signaling pathways in JIA polarized T1 cells. The polarized JIA T1 cells were comprised of Th and Tc cells, with Th cells producing IFNγ (Th1), IL-17 (Th17), and both IFNγ-IL-17 (Th1.17) and Tc cells producing IFNγ (Tc1). The JIA polarized CD4+ T1 cells expressed both Tbet and RORγT, with higher expression of the transcription factors associated with higher frequency of IL-17 producing cells. T1 polarized naïve CD4+ cells from JIA also produced more IFNγ and more IL-17 than HC. We show that in JIA T1 polarization inappropriately generates Th1, Th17, and Th1.17 cells. Our data provides a tool for studying the development of heterogeneous inflammatory T cells in JIA under T1 polarizing conditions and for identifying pathogenic immune cells that are important as drug targets and diagnostic markers.
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影响因子：
14.9
作者：
Gene Ontology Consortium
通讯作者：
Gene Ontology Consortium
DOI：
10.1084/jem.20070663
发表时间：
2007-08-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Annunziato F;Cosmi L;Santarlasci V;Maggi L;Liotta F;Mazzinghi B;Parente E;Filì L;Ferri S;Frosali F;Giudici F;Romagnani P;Parronchi P;Tonelli F;Maggi E;Romagnani S
通讯作者：
Romagnani S
影响因子：
--
作者：
Cosmi, Lorenzo;Cimaz, Rolando;Annunziato, Francesco
通讯作者：
Annunziato, Francesco
影响因子：
8
作者：
Henderson, Lauren A.;Hoyt, Kacie J.;Nigrovic, Peter A.
通讯作者：
Nigrovic, Peter A.
影响因子：
14.2
作者：
Annunziato, Francesco;Romagnani, Chiara;Romagnani, Sergio
通讯作者：
Romagnani, Sergio