CX3CR1+c-kit+ Bone Marrow Cells Give Rise to CD103+ and CD103- Dendritic Cells with Distinct Functional Properties

CX3CR1+c-kit+ Bone Marrow Cells Give Rise to CD103+ and CD103- Dendritic Cells with Distinct Functional Properties
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DOI:
10.4049/jimmunol.181.9.6178
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发表时间:
2008-11-01
影响因子:
4.4
通讯作者:
Foerster, Reinhold
Foerster, Reinhold
中科院分区:
医学2区
文献类型:
--
作者:
del Rio, Maria-Luisa;Rodriguez-Barbosa, Jose-Ignacio;Foerster, Reinhold

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树突状细胞(DC)在形态、表型和功能方面呈现出相当异质的细胞群,并且像免疫系统的大多数细胞一样,经历着持续的更新过程。CD103⁺(整合素α(E))DC已被确定为一种主要的黏膜DC亚群,参与诱导T细胞上的组织特异性归巢分子,但对于能够补充该DC亚群的祖细胞知之甚少。在此我们报道,谱系(lin)⁻CX₃CR1⁺c - kit⁺(GFP⁺c - kit⁺)骨髓细胞能够在体外和体内分化为CD11c⁺CD103⁻或CD11c⁺CD103⁺ DC。基因表达以及功能测定揭示了体外产生的这两种亚群具有不同的表型和功能特性。CD103⁻ DC表现出增强的吞噬作用,并通过分泌促炎细胞因子对脂多糖(LPS)刺激作出反应,而CD103⁺ DC表达高水平的共刺激分子并能有效诱导同种异体T细胞增殖。在将GFP⁺c - kit⁺骨髓细胞过继转移给接受过敏性肺部炎症照射的受体后,我们在肺以及引流肺的支气管淋巴结中鉴定出来自供体的CD103⁺ DC。总之,这些数据表明GFP⁺c - kit⁺细胞有助于淋巴器官和非淋巴器官中CD103⁺ DC的补充。《免疫学杂志》,2008年,181卷:6178 - 6188页。
Dendritic cells (DC) represent a rather heterogeneous cell population with regard to morphology, phenotype, and function and, like most cells of the immune system, are subjected to a continuous renewal process. CD103(+) (integrin alpha(E)) DC have been identified as a major mucosal DC subset involved in the induction of tissue-specific homing molecules on T cells, but little is known about progenitors able to replenish this DC subset. Herein we report that lineage (lin)(-)CX(3)CR1(+)c-kit(+) (GFP(+)c-kit(+)) bone marrow cells can differentiate to either CD11c(+)CD103(-) or CD11c(+)CD103(+) DC in vitro and in vivo. Gene expression as well as functional assays reveal distinct phenotypical and functional properties of both subsets generated in vitro. CD103(-) DC exhibit enhanced phagocytosis and respond to LPS stimulation by secreting proinflammatory cytokines, whereas CD103(+) DC express high levels of costimulatory molecules and efficiently induce allogeneic T cell proliferation. Following adoptive transfer of GFP(+)c-kit(+) bone marrow cells to irradiated recipients undergoing allergic lung inflammation, we identified donor-derived CD103(+) DC in lung and the lung-draining bronchial lymph node. Collectively, these data indicate that GFP(+)c-kit(+) cells contribute to the replenishment of CD103+ DC in lymphoid and nonlymphoid organs. The Journal of Immunology, 2008, 181: 6178-6188.