CXCL13 production by an established lymph node stromal cell line via lymphotoxin-beta receptor engagement involves the cooperation of multiple signaling pathways.
CXCL13 production by an established lymph node stromal cell line via lymphotoxin-beta receptor engagement involves the cooperation of multiple signaling pathways.
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DOI：
10.1093/intimm/dxp014
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发表时间：
2009-04
影响因子：
4.4
通讯作者：
H. Suto;T. Katakai;M. Sugai;T. Kinashi;A. Shimizu
中科院分区：
文献类型：
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作者：
H. Suto;T. Katakai;M. Sugai;T. Kinashi;A. Shimizu
次级淋巴器官中的非造血间充质基质细胞通过表现出诸如产生淋巴稳态趋化因子的专门特征而在组织和免疫应答中发挥关键作用。然而，基质细胞的成熟过程中介导的光敏素β受体（LT β R）信号，基质成熟的关键，仍然不清楚。利用从小鼠淋巴结建立的基质细胞系，其可以通过LT β R而不是肿瘤坏死因子（TNF）受体（TNFR）的参与产生稳态趋化因子CXC趋化因子配体（CXCL）13，我们分析了成熟过程中细胞内信号传导事件的细节。经典和非经典核因子-κ B（NF-κ B）途径的激活对于CXCL 13诱导是必不可少的;然而，过量的非经典RelB-p52复合物仍然不足以促进CXCL 13基因表达。在RelB-p52过表达的条件下，TNF α可以诱导显著高量的CXCL 13产生，表明TNFR的下游含有额外的信号传导的关键组分。我们还发现，除了NF-κ B通路，蛋白激酶C活性在这一过程中起着关键作用。综上所述，这表明LT β R介导的淋巴基质细胞的成熟是通过多个信号级联的合作来完成的。
Non-hematopoietic mesenchymal stromal cells in secondary lymphoid organs play pivotal roles in tissue organization and immune responses by exhibiting specialized features such as the production of lymphoid homeostatic chemokines. However, the maturational process of stromal cells mediated by lymphotoxin-beta receptor (LTbetaR) signaling, a key for stromal maturation, remains unclear. Taking advantage of a stromal cell line established from mouse lymph node, which can produce a homeostatic chemokine, CXC chemokine ligand (CXCL) 13, by the engagement of LTbetaR but not by tumor necrosis factor (TNF) receptor (TNFR), we analyzed the details of intracellular signaling events during the maturational process. The activation of both canonical and non-canonical nuclear factor-kappaB (NF-kappaB) pathways was essential for CXCL13 induction; however, an excessive amount of non-canonical RelB-p52 complex was still insufficient for CXCL13 gene expression. Under RelB-p52-over-expressed conditions, TNFalpha could induce a markedly high amount of CXCL13 production, indicating that the downstream of TNFR contains an additional key component of signaling. We also found that protein kinase C activity plays a critical role in this process in addition to the NF-kappaB pathways. Taken together, it is suggested that the maturation of lymphoid stromal cells mediated by LTbetaR is accomplished by the cooperation of multiple signaling cascades.