Toll-like receptor 3 in nasal CD103+ dendritic cells is involved in immunoglobulin A production
Toll-like receptor 3 in nasal CD103+ dendritic cells is involved in immunoglobulin A production
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鼻 CD103 树突状细胞中的 Toll 样受体 3 参与免疫球蛋白 A 的产生
DOI：
10.1038/mi.2017.48
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发表时间：
2017
影响因子：
8
通讯作者：
Seya T
中科院分区：
文献类型：
--
作者：
Takaki H;Kure S;Oshiumi H;Sakoda Y;Suzuki T;Ainai A;Hasegawa H;Matsumoto M;Seya T
鼻腔接种流感血凝素亚单位的聚肌苷-多胞苷(PolyI：C)，一种合成的双链RNA类似物，可促进疫苗特异性免疫球蛋白(Ig)A的产生，在预防免疫方面优于免疫球蛋白。在小鼠模型中，研究了PolyI：C偏斜于鼻腔相关淋巴组织(NALT)中IgA产生的机制。鼻腔内滴注PolyI：C内吞CD103+树突状细胞(DC)，诱导T细胞活化，包括产生干扰素-γ。根据基因敲除小鼠的研究，PolyI：C通过适配器TICAM-1(也称为TRIF)激活Toll样受体3信号，主要导致T细胞依赖的IgA产生。在PolyI：C刺激下，鼻腔CD103+DC可激活转化生长因子-β信号通路和激活诱导型胞苷脱氨酶。在CD103+DC缺陷的BATF3−/−小鼠中，免疫球蛋白A而不是免疫球蛋白的产生受到损害。IgA产生细胞的基因组重组与PolyI：C刺激的DC和鼻腔微环境有关。PolyI：C诱导B细胞活化因子表达，弱触发T细胞非依赖性IgA的产生。PolyI：C同时激活线粒体抗病毒信号通路，然后激活I型干扰素受体通路，这些通路只最小程度地参与IgA的产生。综上所述，NALT中的CD103+DC对于PolyI：C在增强疫苗特异性IgA诱导和对流感病毒的保护性免疫方面的佐剂活性是不可或缺的。
Intranasal inoculation with influenza hemagglutinin subunit with polyinosine-polycytidylic (polyI: C), a synthetic analog for double-stranded RNA, enhances production of vaccine-specific immunoglobulin (Ig) A, which is superior to IgG in prophylactic immunity. The mechanism whereby polyI: C skews to IgA production in the nasal-associated lymph tissue (NALT) was investigated in mouse models. Nasally instilled polyI: C was endocytosed into CD103+ dendritic cells (DCs) and induced T-cell activation, including interferon (IFN)-γ production. According to knockout mouse studies, polyI: C activated the Toll-like receptor 3 signal via the adapter TICAM-1 (also called TRIF), that mainly caused T-cell-dependent IgA production. Nasal CD103+ DCs activated transforming growth factor-β signaling and activation-induced cytidine deaminase upon polyI: C stimulation. IgA rather than IgG production was impaired in Batf3−/− mice, where CD103+ DCs are defective. Genomic recombination occurred in IgA-producing cells in association with polyI: C-stimulated DCs and nasal microenvironment. PolyI: C induced B-cell-activating factor expression and weakly triggered T-cell-independent IgA production. PolyI: C simultaneously activated mitochondrial antiviral signaling and then type I IFN receptor pathways, which only minimally participated in IgA production. Taken together, CD103+ DCs in NALT are indispensable for the adjuvant activity of polyI: C in enhancing vaccine-specific IgA induction and protective immunity against influenza viruses.