A Single Microorganism Epitope Attenuates the Development of Murine Autoimmune Arthritis: Regulation of Dendritic Cells via the Mannose Receptor.
A Single Microorganism Epitope Attenuates the Development of Murine Autoimmune Arthritis: Regulation of Dendritic Cells via the Mannose Receptor.
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DOI：
10.3389/fimmu.2018.01528
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发表时间：
2018
影响因子：
7.3
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Yang F;Fan X;Huang H;Dang Q;Lei H;Li Y
来自硕大利什曼原虫的活化C激酶（LACK）受体的利什曼原虫类似物的单个表位，即多肽LACK 156 -173，被Vβ4+/Vα8+ T细胞识别，并激活这些细胞，驱动随后的T辅助细胞（Th）2应答。本研究旨在研究LACK 156 -173表位在小鼠自身免疫性关节炎模型中的治疗潜力。为了探索LACK 156 -173表位对鼠胶原抗体诱导的关节炎的影响，以及其免疫学机制，我们用LACK 156 -173表位表达质粒或多肽接种或处理小鼠。然后通过临床评分、组织病理学和定量实时聚合酶链反应（qRT-PCR）分析评估LACK 156 -173表位的作用。使用流式细胞仪，我们测量了CD 11 c+树突状细胞（DC）的亚群和成熟度，以及T细胞极化，在共培养实验中。我们还测量了细胞因子基因的表达和产生。鼠巨噬细胞样细胞系RAW264.7用于鉴定表位的受体。用LACK 156 -173表位表达质粒或多肽接种或治疗小鼠改善了关节炎的严重程度。qRT-PCR分析显示，与未治疗的关节炎对照相比，LACK 156 -173表位改善了滑膜组织中效应T细胞的平衡。Toll样受体（TLR）4表达被LACK 156 -173减弱。该表位还通过调节CD 11 c + DCs的分化、成熟和功能以及上调Jagged 1配体表达来影响T细胞极化。阻断甘露糖受体（MR）显著减弱LACK 156 -173表位诱导的巨噬细胞活化。我们的数据表明，接种疫苗或用单一微生物表位LACK 156 -173治疗是对鼠自身免疫性关节炎的高效疗法。通过MR调节DC的分化、成熟和功能，导致Jagged 1表达上调和Th 2细胞极化，从而介导治疗效果。我们的结果证明了LACK 156 -173表位在类风湿性关节炎中的治疗潜力。
A single epitope of Leishmania analog of the receptors for activated C kinase (LACK) from Leishmania major, the polypeptide LACK156–173, is recognized by Vβ4+/Vα8+ T cells, and activate these cells that drives the subsequent T helper (Th)2 response. This study was undertaken to investigate the therapeutic potential of the LACK156–173 epitope in murine autoimmune arthritis models. To explore the influence of the LACK156–173 epitope on murine collagen antibody-induced arthritis, as well as its immunological mechanism, we vaccinated or treated mice with a LACK156–173 epitope expression plasmid or polypeptide. The effect of LACK156–173 epitope was then evaluated by clinical scores, histopathology, and quantitative real-time polymerase chain reaction (qRT-PCR) analysis. Using flow cytometry, we measured the subsets and maturity of CD11c+ dendritic cells (DCs), as well as T cell polarization, in co-culture experiments. We also measured cytokine gene expression and production. The murine macrophage-like cell line RAW264.7 was used to identify the receptor for the epitope. Vaccination or treatment of the mice with the LACK156–173 epitope expression plasmid or polypeptide ameliorated the severity of arthritis. qRT-PCR analysis revealed that the LACK156–173 epitope improved the balance of effector T cells in synovial tissue compared to that in untreated arthritis controls. Toll-like receptor (TLR) 4 expression was diminished by LACK156–173. The epitope also influenced T cell polarization by regulating the differentiation, maturation, and functions of CD11c+ DCs and upregulating Jagged1 ligand expression. Blocking the mannose receptor (MR) significantly attenuated LACK156–173 epitope-induced macrophage activation. Our data indicate that vaccination or treatment with a single microorganism epitope, LACK156–173, is a highly efficient therapy for murine autoimmune arthritis. The therapeutic effects are mediated by the regulation of the differentiation, maturation, and functions of DCs via MR, resulting in the upregulation of Jagged1 expression and Th2 cell polarization. Our results demonstrate the therapeutic potential of the LACK156–173 epitope in rheumatoid arthritis.
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法配体的改变揭示了T细胞对病原表位的响应中的可塑性有限。
影响因子：
15.3
作者：
Pingel, S;Launois, P;Fowell, D J;Turck, C W;Southwood, S;Sette, A;Glaichenhaus, N;Louis, J A;Locksley, R M
通讯作者：
Locksley, R M
影响因子：
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作者：
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通讯作者：
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影响因子：
4.6
作者：
Motomura, Y.;Wang, H.;Khan, W. I.
通讯作者：
Khan, W. I.
影响因子：
6.4
作者：
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通讯作者：
Mitre, Edward
影响因子：
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作者：
Lin, Chu-Lun;Hsiao, George;Lee, Yueh-Lun
通讯作者：
Lee, Yueh-Lun