Central role of conventional dendritic cells in regulation of bone marrow release and survival of neutrophils.

Central role of conventional dendritic cells in regulation of bone marrow release and survival of neutrophils.
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常规树突状细胞在调节中性粒细胞骨髓释放和存活中的核心作用。

DOI:
10.4049/jimmunol.1300237
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发表时间:
2014-04-01
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Aloman C
Aloman C
中科院分区:
其他
文献类型:
--
作者:
Jiao J;Dragomir AC;Kocabayoglu P;Rahman AH;Chow A;Hashimoto D;Leboeuf M;Kraus T;Moran T;Carrasco-Avino G;Friedman SL;Merad M;Aloman C

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中性粒细胞是免疫系统中最丰富的细胞类型,在先天性免疫应答中发挥重要作用。使用各种各样的小鼠模型,无论是有缺陷的DC发展或条件性DC耗竭,我们提供了在体内的证据表明,传统的树突状细胞(cDC)在中性粒细胞的稳态调节中发挥重要作用。Flk 2、Flt 3L和Batf 3基因敲除小鼠在DC发育方面存在缺陷,在稳态下肝脏中性粒细胞数量增加。相反,在DC特异性PTEN敲除小鼠中,中性粒细胞频率降低,其具有CD 8+和CD 103 + DC的扩增。在嵌合CD 11 c-DTR小鼠中,cDC耗竭导致在不存在组织学炎症或促炎细胞因子增加的情况下外周器官中中性粒细胞的全身性增加。这种效应也存在于脾切除的嵌合CD 11 c-DTR小鼠中,而在骨髓50%正常的嵌合小鼠中则不存在。在嵌合CD 11 c-DTR小鼠中,DT治疗导致中性粒细胞从骨髓进入循环的运输增强和中性粒细胞募集增加。此外,存在参与中性粒细胞稳态的趋化因子/细胞因子的表达增加和中性粒细胞凋亡减少。这些数据强调了DC池在调节非淋巴器官中中性粒细胞室中的作用。
Neutrophils are the most abundant cell type in the immune system and play an important role in the innate immune response. Using a diverse range of mouse models with either defective DC development or conditional DC depletion, we provide in vivo evidence indicating that conventional dendritic cells (cDC) play an important role in the regulation of neutrophil homeostasis. Flk2, Flt3L and Batf3 knockout mice, which have defects in DC development, have increased numbers of liver neutrophils in the steady state. Conversely, neutrophil frequency is reduced in DC-specific PTEN knockout mice, which have an expansion of CD8+ and CD103+ DCs. In chimeric CD11c-DTR mice, cDC depletion results in a systemic increase of neutrophils in peripheral organs in the absence of histological inflammation or an increase in pro-inflammatory cytokines. This effect is also present in splenectomized chimeric CD11c-DTR mice and is absent in chimeric mice with 50% normal bone marrow. In chimeric CD11c-DTR mice, DT treatment results in enhanced neutrophil trafficking from the bone marrow into circulation and increased neutrophil recruitment. Moreover, there is an increased expression of chemokines/cytokines involved in neutrophil homeostasis and reduced neutrophil apoptosis. These data underscore the role of the DC pool in regulating the neutrophil compartment in non-lymphoid organs.
树突状细胞的组成型消融会破坏CD4 T细胞的自耐力,并导致自发性致命自身免疫性。
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