Role of CCL17 in the Generation of Cutaneous Inflammatory Reactions in Hu-PBMC-SCID Mice Grafted with Human Skin
Role of CCL17 in the Generation of Cutaneous Inflammatory Reactions in Hu-PBMC-SCID Mice Grafted with Human Skin
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DOI：
10.1038/jid.2008.333
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发表时间：
2009-04-01
影响因子：
6.5
通讯作者：
Tsicopoulos, Anne
中科院分区：
文献类型：
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作者：
Gilet, Jules;Chang, Ying;Tsicopoulos, Anne
CCL17 可能对皮肤炎症感兴趣，因为它主要吸引表达皮肤归巢受体的 T 细胞并结合优先在 Th-2 细胞上表达的趋化因子受体 CCR4。我们在人源化小鼠模型中评估了 CCL17 注射的体内效果。将I-125-CCL17注射到用外周血单核细胞重建的严重联合免疫缺陷（SCID）小鼠移植的人皮肤中，导致CCL17从皮肤快速转运至同侧淋巴结，3小时后，淋巴结中出现人记忆CD4（+）细胞和树突状细胞浸润。 24小时后，皮内注射CCL17导致人类记忆CD4(+)细胞、单核细胞和嗜碱性粒细胞以及小鼠嗜酸性粒细胞在皮肤中募集。在用极化的 Th-1 或 Th-2 细胞重建的 SCID 小鼠中，皮内注射 CCL17 导致招募 IL-4(+) Th-2 细胞，但不招募 IFN-gamma(+) Th-1 细胞，而 CCL17 能够在体外招募这两种细胞亚群。这些结果表明，在人源化体内模型中，CCL17本身足以诱导淋巴结募集记忆CD4(+)和树突状细胞以及皮肤募集Th-2型细胞，强调其在Th-2相关皮肤炎症的发生和发展中发挥着重要作用。
CCL17 may be of interest in skin inflammation, because it mainly attracts T cells expressing the cutaneous homing receptor and binds the chemokine receptor CCR4, preferentially expressed on Th-2 cells. We evaluated the in vivo effect of CCL17 injection in a humanized mouse model. I-125-CCL17 injection into human skin grafted on severe combined immunodeficient (SCID) mice reconstituted with peripheral blood mononuclear cells resulted in a rapid transportation of CCL17 from the skin to the homolateral lymph nodes, followed 3 hours later by a lymph node infiltration of human memory CD4(+) cells and dendritic cells. Intradermal injection of CCL17 resulted 24 hours later in a cutaneous recruitment of human memory CD4(+) cells, monocytes, and basophils, but also murine eosinophils. In SCID mice reconstituted with polarized Th-1 or Th-2 cells, intradermal injection of CCL17 resulted in the recruitment of IL-4(+) Th-2 cells but not of IFN-gamma(+) Th-1 cells, whereas CCL17 was able to recruit both subsets in vitro. These results suggest that, in a humanized in vivo model, CCL17 is sufficient per se to induce a lymph node recruitment of memory CD4(+) and dendritic cells and a cutaneous recruitment of Th-2-type cells, stressing it as an important actor in the initiation and development of Th-2-associated skin inflammation.