TLR9-and FcεRI-mediated responses oppose one another in plasmacytoid dendritic cells by down-regulating receptor expression
TLR9-and FcεRI-mediated responses oppose one another in plasmacytoid dendritic cells by down-regulating receptor expression
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DOI：
10.4049/jimmunol.175.9.5724
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发表时间：
2005-11-01
影响因子：
4.4
通讯作者：
Liu, MC
中科院分区：
文献类型：
--
作者：
Schroeder, JT;Bieneman, AP;Liu, MC
浆细胞样树突状细胞（pDC）不仅表达TLR9分子，通过与CpG DNA的连接促进Th1反应，而且还具有参与过敏原呈现和诱导Th2反应的IgE受体（Fe epsilon RI）。这种二分法促使研究确定TLR9和IgE受体介导的反应是否通过影响受体表达和相关功能反应而在pDC中相互对立。结果表明，在CpG寡脱氧核苷酸(ODN)-2216刺激下，IgE交联降低了pDC细胞的TLR9，抑制了这些细胞分泌ifn - α的能力。相比之下，在首次暴露于TLR9与ODN-2216连接的pDC中，Fc epsilon Ri α mRNA减少了15倍，表面蛋白丢失。结果表明，I型IFNs部分介导了这种作用，因为rIFN-a也导致Fc epsilon RI α mRNA减少了4倍。最后，ODN-2216介导的FC ε - RI α的减少与过敏原诱导的CD4(+) T细胞增殖的选择性抑制相关，但与破伤风类毒素引起的反应无关。总的来说，这些结果暗示了特异性先天免疫反应和ige依赖性免疫反应在树突状细胞水平上相互拮抗的机制，并可能对随后的反应是Th1还是Th2产生重大影响。
Plasmacytoid dendritic cells (pDC) express not only TLR9 molecules through which ligation with CpG DNA favors Th1 responses but also possess IgE receptors (Fe epsilon RI) implicated in allergen presentation and induction of Th2 responses. This dichotomy prompted an investigation to determine whether TLR9- and IgE receptor-mediated responses oppose one another in pDC by affecting receptor expression and associated functional responses. Results showed that IgE cross-linking reduced TLR9 in pDC and inhibited the, capacity of these cells to secrete IFN-alpha when stimulated with the CpG oligodeoxynucleotide (ODN)-2216. In contrast, an similar to 15-fold reduction in Fc epsilon Ri alpha mRNA and a loss in surface protein were seen in pDC first exposed to TLR9 ligation with ODN-2216. Results indicated that type I IFNs partly mediated this effect, as rIFN-a also caused a significant similar to 4-fold reduction in Fc epsilon RI alpha mRNA. Finally, this reduction in FC epsilon RI alpha mediated by ODN-2216 correlated with a selective suppression of allergen-induced CD4(+) T cell proliferation, but not of responses resulting from tetanus toxoid. Overall, these results imply mechanisms by which specific innate and IgE-dependent immune responses counterregulate one another at the dendritic cell level and may have significant impact on whether an ensuing response is either of Th1 or Th2 in nature.