期刊
JOURNAL OF IMMUNOLOGY
卷 202, 期 10, 页码 2999-3007出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1801578
关键词
-
类别
资金
- National Natural Science Foundation of China [31570888, 81671537]
- Youth Innovation Promotion Association Chinese Academy of Sciences [2016089]
- Beijing Natural Science Foundation [7164277]
The lymphatic vasculature is an important route for dendritic cell (DC) or tumor cell migration from peripheral tissues to draining lymph nodes (DLNs). However, the underlying molecular and cellular mechanisms remain poorly understood. In this study, using conventional bone marrow chimeric mice and additional UVB radiation, we found that deficiency of LIGHT but not lymphotoxin (LT) alpha 1 beta 2, likely on radioresistant Langerhans cells (LCs), resulted in impaired skin DC migration to DLNs during LPS-induced inflammation. In addition, LT beta receptor (LT beta R), but not herpes virus entry mediator, was found to be the receptor of LIGHT controlling DC migration. Furthermore, conditional deficiency of LT beta R in Tie2(cre) or Lyve1(cre) mice, but not in LT beta R-deficient bone marrow chimeric mice, impaired DC migration, suggesting an important role of LT beta R in radioresistant lymphatic endothelial cells (LECs), although the role of LT beta R in blood endothelial cells remains intriguing. Mechanistically, the gene expression of both CCL21 and CCL19 was found to be reduced in skin LECs isolated from LC-LIGHT-conditionally deficient or Lyve1(cre)Ltbr(fl/fl) mice compared with their controls upon LPS stimulation. Soluble recombinant LIGHT was able to upregulate CCL21 and CCL19 gene expression on SVEC4-10 endothelial cells. Doxycycline, an inhibitor of soluble LIGHT release in the inflamed skin, impaired skin CCL21 and CCL19 expression and DC migration. In addition, melanoma cell metastasis to DLNs was also inhibited in LC-LIGHT-conditionally deficient or Lyve1(cre)Ltbr(fl/fl) mice. Together, our data suggest, to our knowledge, a previously unrecognized scenario in which LCs activate LECs via the LIGHT-LT beta R signaling axis to promote DC migration or tumor cell metastasis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据