B lymphocyte stimulator regulates adaptive immune responses by directly promoting dendritic cell maturation
B lymphocyte stimulator regulates adaptive immune responses by directly promoting dendritic cell maturation
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DOI：
10.4049/jimmunol.180.11.7394
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发表时间：
2008-06-01
影响因子：
4.4
通讯作者：
Jelinek, Diane F.
中科院分区：
文献类型：
--
作者：
Chang, Sook Kyung;Mihalcik, Stephen A.;Jelinek, Diane F.
B淋巴细胞刺激因子（BLyS）是适应性免疫细胞，特别是B谱系细胞的众所周知的直接共刺激因子。然而，我们最近报道BLyS也能够激活单核细胞。其他先天性免疫细胞，如树突状细胞（DC），在适应性免疫应答的启动中发挥关键作用，本研究的目的是评估BLyS是否在调节人DC功能中具有直接作用。在这项研究中，我们表明BLyS诱导DC激活和成熟。因此，BLyS强烈诱导上调表面共刺激分子的表达和特定的细胞因子和趋化因子在DC中的分泌。BLyS刺激的I）C（BLyS-DC）也能够比对照I）C更大程度地增加同种异体CD 4 T细胞增殖。BLyS-DC分泌升高水平的主要Th 1极化细胞因子IL-12 p70，并且它们促进幼稚CD 4 T细胞分化为Th 1 T细胞。关于BLyS受体表达，DC主要表达细胞质跨膜激活因子和CAML相互作用因子;然而，也表达低水平的细胞表面跨膜激活因子和CAML相互作用因子。总的来说，我们的数据表明BLyS可以通过诱导DC成熟间接调节适应性免疫细胞。
B lymphocyte stimulator (BLyS) is a well-known direct costimulator of adaptive immune cells, particularly B lineage cells. However, we have reported recently that BLyS is also able to activate monocytes. Other innate immune cells, such as dendritic cells (DCs), play a key role in the initiation of adaptive immune responses and the purpose of the current study was to assess whether there is a direct role for BLyS in modulating human DC functions. In this study, we show that BLyS induces DC activation and maturation. Thus, BLyS strongly induced up-regulation of surface costimulatory molecule expression and secretion of specific cytokines and chemokines in DCs. BLyS-stimulated I)Cs (BLyS-DCs) were also able to augment allogeneic CD4 T cell proliferation to a greater extent than control I)Cs. BLyS-DCs secreted elevated levels of the major Th1-polarizing cytokine, IL-12p70, and they promoted naive CD4 T cell differentiation into Th1 T cells. Regarding BLyS receptor expression, DCs primarily express cytoplasmic transmembrane activator and CAML interactor; however, low levels of cell surface transmembrane activator and CAML interactor are expressed as well. Collectively, our data suggest that BLyS may modulate adaptive immune cells indirectly by inducing DC maturation.