A stroma-derived defect in NF-κB2-/- mice causes impaired lymph node development and lymphocyte recruitment
A stroma-derived defect in NF-κB2-/- mice causes impaired lymph node development and lymphocyte recruitment
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DOI：
10.4049/jimmunol.173.4.2271
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发表时间：
2004-08-15
影响因子：
4.4
通讯作者：
Caamaño, J
中科院分区：
文献类型：
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作者：
Carragher, D;Johal, R;Caamaño, J
NF-kappaB转录因子家族在免疫环境的造血和基质区室的免疫功能和调节的各个方面都是至关重要的。最近对缺乏NF-kappaB家族特定成员的小鼠模型的研究揭示了这些蛋白在继发性淋巴组织器官发生过程中的关键作用。在这项研究中，我们研究了NF-kappaB家族成员NF-kappaB2在淋巴结发育和淋巴细胞募集中的作用。nfkappab2（-/-）小鼠腹股沟淋巴结的大小和细胞数量减少，最明显的是在B细胞室。通过体外和体内淋巴结移植试验，我们发现这种缺陷存在于基质室中。进一步检查nfkappab2（-/-）腹股沟淋巴结发现外周淋巴结定位蛋白组分CD34和糖基化依赖性细胞粘附分子-1以及内皮小静脉限制性高硫转移酶HEC-GlcNAc6ST的表达明显降低。此外，淋巴细胞归巢趋化因子CCL19、CCL21和CXCL13的表达下调。这些数据强调了NF-kappaB2在腹股沟淋巴结器官发生和淋巴细胞募集中的作用，由于其上调必需细胞粘附分子和趋化因子的作用，同时提示NF-kappaB2在淋巴结内皮组织中的潜在作用。
The NF-kappaB family of transcription factors is vital to all aspects of immune function and regulation in both the hemopoietic and stromal compartments of immune environments. Recent studies of mouse models deficient for specific members of the NF-kappaB family have revealed critical roles for these proteins in the process of secondary lymphoid tissue organogenesis. In this study, we investigate the role of NF-kappaB family member NF-kappaB2 in lymph node development and lymphocyte recruitment. Inguinal lymph nodes in nfkappab2(-/-) mice are reduced in size and cellularity, most notably in the B cell compartment. Using in vitro and in vivo lymph node grafting assays, we show that the defect resides in the stromal compartment. Further examination of the nfkappab2(-/-) inguinal lymph nodes revealed that expression of peripheral node addressin components CD34 and glycosylation-dependent cell adhesion molecule-1 along with the high endothelial venule-restricted sulfoltransferase HEC-GlcNAc6ST was markedly reduced. Furthermore, expression of the lymphocyte homing chemokines CCL19, CCL21, and CXCL13 was down-regulated. These data highlight the role of NF-kappaB2 in inguinal lymph node organogenesis and recruitment of lymphocytes to these organs due to its role in up-regulation of essential cell adhesion molecules and chemokines, while suggesting a potential role for NF-kappaB2 in organization of lymph node endothelium.