Meuter Simone, Schaerli Patrick, Roos Regula Stuber, Brandau Oliver, Bösl Michael R, von Andrian Ulrich H, Moser Bernhard
Department of Medical Biochemistry and Immunology, Henry Wellcome Building, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, United Kingdom.
Mol Cell Biol. 2007 Feb;27(3):983-92. doi: 10.1128/MCB.01648-06. Epub 2006 Nov 27.
Dendritic cells (DCs) have long been recognized as key regulators of immune responses. However, the process of their recruitment to peripheral tissues and turnover during homeostasis remains largely unknown. The chemokine CXCL14 (BRAK) is constitutively expressed in skin and other epithelial tissues. Recently, the human chemokine was proposed to play a role in the homeostatic recruitment of macrophage and/or DC precursors toward the periphery, such as skin. Although so far no physiological function could be demonstrated for the murine CXCL14, it shows a remarkable homology to the human chemokine. In order to elucidate the in vivo role of CXCL14, we generated a mouse defective for this chemokine. We studied various components of the immune system with emphasis on monocytes/macrophages and DC/Langerhans cell (LC) populations in different tissues during steady state but did not find a significant difference between knockout (CXCL14(-)(/)(-)) and control mice. Functionally, LCs were able to become activated, to migrate out of skin, and to elicit a delayed type of hypersensitivity reaction. Overall, our data indicate that murine CXCL14 is dispensable for the homeostatic recruitment of antigen-presenting cells toward the periphery and for LC functionality.
树突状细胞(DCs)长期以来一直被认为是免疫反应的关键调节因子。然而,它们在稳态期间募集到外周组织以及更新的过程在很大程度上仍不清楚。趋化因子CXCL14(BRAK)在皮肤和其他上皮组织中组成性表达。最近,有人提出这种人类趋化因子在巨噬细胞和/或DC前体向皮肤等外周组织的稳态募集中发挥作用。尽管到目前为止尚未证明小鼠CXCL14具有生理功能,但它与人类趋化因子具有显著的同源性。为了阐明CXCL14在体内的作用,我们培育出了一种缺乏这种趋化因子的小鼠。我们研究了免疫系统的各种成分,重点关注稳态期间不同组织中的单核细胞/巨噬细胞以及DC/朗格汉斯细胞(LC)群体,但未发现基因敲除小鼠(CXCL14(-)(/)(-))与对照小鼠之间存在显著差异。在功能上,LC能够被激活、从皮肤中迁移出来,并引发迟发型超敏反应。总体而言,我们的数据表明,小鼠CXCL14对于抗原呈递细胞向外周组织的稳态募集以及LC的功能并非必不可少。