淋巴毒素-β受体信号传导是肝外胆管分化和功能稳态控制所必需的。

Lymphotoxin-beta receptor signaling is required for the homeostatic control of HEV differentiation and function.

作者信息

Browning Jeffrey L, Allaire Norm, Ngam-Ek Apinya, Notidis Evangelia, Hunt Jane, Perrin Steven, Fava Roy A

机构信息

Department of Immunobiology, Biogen Idec, Cambridge, Massachusetts 02142, USA.

出版信息

Immunity. 2005 Nov;23(5):539-50. doi: 10.1016/j.immuni.2005.10.002.

DOI:10.1016/j.immuni.2005.10.002

PMID:16286021

Abstract

The lymphotoxin axis is important for the maintenance of several specialized lymphoid microenvironments in secondary lymphoid tissue. Lymphoid-tissue architecture is highly plastic and requires continual homeostatic signaling to maintain its basal functional state. The cellularity of lymph nodes in adult mice was reduced by systemic blockade of lymphotoxin-beta receptor (LTbeta R) signaling with a soluble decoy receptor both in resting and reactive settings. This reduction in cellularity resulted from greatly impaired lymphocyte entry into lymph nodes due to decreased levels of peripheral lymph node addressing (PNAd) and MAdCAM on high endothelial venules (HEV). LTbeta R signaling was required to maintain normal levels of RNA expression of MAdCAM, and also of PNAd by regulating the expression of key enzymes and scaffold proteins required for its assembly. Thus, the homeostatic maintenance of functional HEV status in adult mice relies largely on LTbeta R signaling.

摘要

淋巴毒素轴对于维持二级淋巴组织中多种特殊淋巴微环境至关重要。淋巴组织结构具有高度可塑性，需要持续的稳态信号来维持其基础功能状态。在静息和反应状态下，用可溶性诱饵受体对淋巴毒素-β受体（LTβR）信号进行全身阻断，均可降低成年小鼠淋巴结的细胞数量。细胞数量的减少是由于高内皮微静脉（HEV）上外周淋巴结地址素（PNAd）和黏膜地址素细胞黏附分子（MAdCAM）水平降低，导致淋巴细胞进入淋巴结的能力大幅受损。LTβR信号传导对于维持MAdCAM的正常RNA表达水平以及通过调节其组装所需的关键酶和支架蛋白的表达来维持PNAd的正常RNA表达水平是必需的。因此，成年小鼠功能性HEV状态的稳态维持在很大程度上依赖于LTβR信号传导。