CXCL12/CXCR4 signaling promotes human thymic dendritic cell survival regulating the Bcl-2/Bax ratio
CXCL12/CXCR4 signaling promotes human thymic dendritic cell survival regulating the Bcl-2/Bax ratio
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DOI：
10.1016/j.imlet.2008.07.006
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发表时间：
2008-09-30
影响因子：
4.4
通讯作者：
Vicente, Angeles
中科院分区：
文献类型：
--
作者：
Hernandez-Lopez, Carmen;Valencia, Jaris;Vicente, Angeles
CXCL12是趋化因子CXC亚家族的成员之一，其生理受体CXCR4在胚胎发育过程中对各种器官的发育至关重要，并参与成体组织中细胞存活、增殖和迁移的控制。在人胸腺中，CXCL12由位于囊下和髓质区域的上皮细胞产生，而CXCR4在不同的胸腺细胞亚群中表达。一些研究结果表明，CXCL12/CXCR4信号参与了不同的胸腺内过程，包括控制人前体细胞的存活和增殖，以及成熟胸腺细胞向外周的出口。在本研究中，我们发现CXCL12也由人胸腺树突状细胞（dc）产生，其中大多数表达CXCR4受体。外源性CXCL12的加入显著抑制了血清耗尽诱导的胸腺dc细胞凋亡，并且使用针对CXCL12或CXCR4的中和抗体治疗降低了它们的存活。CXCL12的促生存作用是通过上调Bcl-2蛋白表达，同时下调Bax蛋白表达介导的。胸腺dc的高活力也增强了它们的异源刺激能力。综上所述，这些结果表明CXCL12在人类胸腺中具有控制胸腺dc存活和功能的新功能。(C) 2008 Elsevier B.V.版权所有
CXCL12, a member of the chemokine CXC subfamily, and its physiologic receptor CXCR4 are essential for the development of various organs during embryonic development and are also involved in the control of cell survival, proliferation and migration in adult tissues. In the human thymus, CXCL12 is produced by epithelial cells located in the subcapsular and medullary regions and CXCR4 is expressed in different thymocyte subpopulations. Several results have demonstrated that CXCL12/CXCR4 signaling participates in different intrathymic processes including the control of human precursor cell survival and proliferation, and the exit of mature thymocytes to the periphery In this study, we show that CXCL12 is also produced by human thymic dendritic cells (DCs), most of which express CXCR4 receptor. The addition of exogenous CXCL12 significantly inhibited the serum depletion-induced apoptosis in thymic DCs, and the treatment with neutralizing antibodies against CXCL12 or CXCR4 decreased their survival. The survival-promoting effect of CXCL12 was mediated by the up-regulation of Bcl-2 protein expression and the concomitant down-regulation of Bax protein expression. The higher viability of thymic DCs also enhanced their allostimulatory capacity. Taken together, the results suggest a new function of CXCL12 in the human thymus controlling the survival and functionality of thymic DCs. (C) 2008 Elsevier B.V. All rights reserved.