Epidermal receptor activator of NF-κB ligand controls Langerhans cells numbers and proliferation
Epidermal receptor activator of NF-κB ligand controls Langerhans cells numbers and proliferation
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DOI：
10.4049/jimmunol.181.2.1103
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发表时间：
2008-07-15
影响因子：
4.4
通讯作者：
Groves, Richard W.
中科院分区：
文献类型：
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作者：
Barbaroux, Jean-Baptiste O.;Beleut, Manfred;Groves, Richard W.
Langerhans细胞（LC）是表皮的树枝状APC种群，它们长期居住并且是自我复制的。这些特征的分子信号尚不清楚。 NF-KAPPA B配体的TNF超家族成员受体激活剂（RankL，TNFSF11）已被证明可维持血液树突状细胞的生存能力，除了其在促进几种细胞类型的增殖和分化中的作用外，还可以维持几种细胞类型的作用。在这项研究中，我们研究了皮肤中RANKL系统的表达，并确定了该分子在LC稳态中的关键作用。在体外和体内，人类KC表达RANKL和表皮LC表达细胞表面等级。在体外，RANKL持续的CD34（ +）祖细胞衍生的LC生存力在无细胞因子培养基中72-H培养后（79.5 +/- 1％和55.2 +/- 5.7％活细胞； n = 4; p <0.05; p <0.05; p <0.05 ）。在体内，RANKL缺陷小鼠表现出明显降低表皮LC密度（507.1 +/- 77.2 vs 873.6 +/- 41.6 LC每毫米（2）; n = 9; p <0.05），并且没有可检测的繁殖力。对凋亡的影响。这些数据表明RANKL系统在调节皮肤内LC存活中的关键作用，并提出KC在维持表皮LC稳态中的调节作用。
Langerhans cells (LC) are the dendritic APC population of the epidermis, where they reside for long periods and are self-replicating. The molecular signals underlying these characteristics are unknown. The TNF superfamily member receptor activator of NF-kappa B ligand (RANKL, TNFSF11) has been shown to sustain viability of blood dendritic cells in addition to its role in promoting proliferation and differentiation of several cell types, notably osteoclasts. In this study, we have studied expression of the RANKL system in skin and have defined a key role for this molecule in LC homeostasis. In vitro and in vivo, human KC expressed RANKL and epidermal LC expressed cell surface RANK. In vitro, RANKL sustained CD34(+) progenitor-derived LC viability following 72-h cultures in cytokine-free medium (79.5 +/- 1 % vs 55.2 +/- 5.7 % live cells, respectively; n = 4; p < 0.05). In vivo, RANKL-deficient mice displayed a marked reduction in epidermal LC density (507.1 +/- 77.2 vs 873.6 +/- 41.6 LC per mm(2); n = 9; p < 0.05) and their proliferation was impaired without a detectable effect on apoptosis. These data indicate a key role for the RANKL system in the regulation of LC survival within the skin and suggest a regulatory role for KC in the maintenance of epidermal LC homeostasis.