Endotoxic shock-expanded murine CD11c low CD45RB + regulatory dendritic cells modulate inflammatory T cell responses through multiple mechanisms.
Endotoxic shock-expanded murine CD11c low CD45RB + regulatory dendritic cells modulate inflammatory T cell responses through multiple mechanisms.
复制标题
内毒素休克扩增小鼠CD11clowCD45RB调节树突状细胞通过多种机制调节炎症T细胞反应
DOI：
10.1038/srep10653
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发表时间：
2015-05-29
影响因子：
4.6
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Wang X;Wang Q;Zhang X;Li Y;Wang J;Hou C;Chen J;Shen B;Shi Y;Zhang J
据报道，树突状细胞（dc）数量和功能的变化在内毒素耐受中起重要作用。据报道，在注射亚致死剂量的脂多糖（LPS）的小鼠中，脾脏CD11clowCD45RB+ dc发生扩增。然而，内毒休克扩展CD11clowCD45RB+ dc的功能尚未得到研究。在这项工作中，我们发现内毒素休克促进具有树突状形态的CD11clowCD45RB+细胞的扩张，并产生低水平的炎症细胞因子和共刺激分子。扩增后的细胞在体外诱导调节性T细胞（Tregs）的产生，表现出不能刺激T细胞和诱导CD4+ T细胞凋亡的能力。与CD11chiCD45RB -常规dc相比，扩增细胞对CD4+ CD25 - T细胞诱导结肠炎具有更好的保护作用，尽管这两个亚群在体内诱导Tregs的能力相似。扩大后的细胞在体内对促炎细胞因子反应的更好控制，与帕氏斑和结肠组织浸润细胞中更多的凋亡有关。因此，扩增的细胞可以通过多种机制调节炎症T细胞反应。我们的研究有助于更好地理解先天免疫反应如何在lps诱导的急性炎症后形成适应性免疫和免疫抑制。
Changes in the number and function of dendritic cells (DCs) have been reported to play an important role in endotoxin tolerance. It has been reported that expansion of splenic CD11clowCD45RB+ DCs occurs in mice injected with sublethal doses of lipopolysaccharide (LPS). However, the function of endotoxic shock-expanded CD11clowCD45RB+ DCs has not been examined. In this work, we show that endotoxic shock promotes the expansion of CD11clowCD45RB+ cells with dendritic morphology and the production of low levels of inflammatory cytokines and costimulatory molecules. The expanded cells induce the generation of regulatory T cells (Tregs), show incapability to stimulate T cells and induce apoptosis of CD4+ T cells in vitro. As compared to CD11chiCD45RB− conventional DCs, the expanded cells exert better protection against colitis induction by CD4+ CD25− T cells, even though both subpopulations show similar ability to induce Tregs in vivo. The better control of proinflammatory cytokine responses in vivo by the expanded cells is associated with more apoptosis in the Payer’s patches and in colonic tissue-infiltrating cells. Thus, the expanded cells can modulate inflammatory T cell responses through multiple mechanisms. Our study facilitates a better understanding how innate immune responses may shape adaptive immunity and immune suppression following LPS-induced acute inflammation.
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DOI：
10.4049/jimmunol.1101180
发表时间：
2011-09-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Gurung P;Rai D;Condotta SA;Babcock JC;Badovinac VP;Griffith TS
通讯作者：
Griffith TS
影响因子：
4.4
作者：
Matsushita, Hidetomo;Ohta, Shoichiro;Izuhara, Kenji
通讯作者：
Izuhara, Kenji
影响因子：
12.8
作者：
Panoutsakopoulou, V;Cantor, H
通讯作者：
Cantor, H
影响因子：
32.4
作者：
Svensson, M;Maroof, A;Kaye, PM
通讯作者：
Kaye, PM
影响因子：
15.3
作者：
Braun, M C;He, J;Wu, C Y;Kelsall, B L
通讯作者：
Kelsall, B L