BDCA-2 signaling inhibits TLR-9-agonist-induced plasmacytoid dendritic cell activation and antigen presentation
BDCA-2 signaling inhibits TLR-9-agonist-induced plasmacytoid dendritic cell activation and antigen presentation
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DOI：
10.1016/j.cellimm.2010.06.005
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发表时间：
2010-01-01
影响因子：
4.3
通讯作者：
Dzionek, Andrzej
中科院分区：
文献类型：
--
作者：
Jaehn, Peter S.;Zaenker, Kurt S.;Dzionek, Andrzej
浆细胞样树突状细胞（PDCs）表达Toll样受体（TLR）9，其介导感染期间微生物DNA或自身免疫性疾病中自身DNA的识别。触发PDC中的TLR-9诱导成熟（溶酶体TLR-9触发）或I型干扰素（IFN-I）产生（内体TLR 9触发）。PDCs还表达BDCA-2（CD 303），这是这些细胞特有的C型凝集素受体（CD 303）。CLRs参与天然免疫和微生物识别，与TLR协同调节炎症反应，抗BDCA-2单克隆抗体可被PDC内化提呈抗原，抑制TLR-9诱导的IFN-Ⅰ表达。在这里，我们研究了在PDC成熟和抗原呈递过程中BDCA-2和TLR-9信号之间的串扰。我们发现，PDCs中BDCA-2诱导的信号传导抑制CpG激活的PDCs中CD 86和CD 40分子的上调，但在CD 40 L激活的PDCs中不抑制。此外，BDCA-2的触发降低了CpG和CD 40 L刺激的PDC处理抗原并将抗原呈递给抗原特异性自体记忆T细胞的能力。该研究表明，BDCA-2是影响两者的IFN-1依赖性自身免疫性疾病的临床免疫治疗的有吸引力的靶点。通过PDC的IFN-1产生和抗原特异性T细胞刺激。(C)2010年爱思唯尔公司All rights reserved.
Plasmacytoid dendritic cells (PDCs) express Toll-like receptor (TLR) 9, which mediates recognition of microbial DNA during infection or self-DNA in autoimmune diseases. Triggering TLR-9 in PDC induces either maturation (lysosomal TLR-9 triggering) or type I interferon (IFN-I) production (endosomal TLR9 triggering). PDCs also express BDCA-2 (CD303), a C-type lectin receptor (CLR) unique to these cells. CLRs appear to function in innate immunity and microbial recognition, and may cooperate with TLRs to fine-tune inflammatory responses.It has been shown that anti-BDCA-2 monoclonal antibody is internalized by PDC for antigen presentation and inhibits TLR-9 induced IFN-I expression. Here we investigated the cross-talk between BDCA-2 and TLR-9-signaling during PDC maturation and antigen presentation. We found that BDCA-2-induced signaling in PDCs inhibits up-regulation of CD86 and CD40 molecules in CpG-activated PDCs, but not in CD40L-activated PDCs. Furthermore, triggering of BDCA-2 diminished the ability of CpG- and CD40L-stimulated PDCs to process and present antigen to antigen-specific autologous memory T cells. This study demonstrates that BDCA-2 represents an attractive target for clinical immunotherapy of IFN-I dependent autoimmune diseases influencing both. IFN-I production and antigen-specific T-cell stimulation by PDC. (C) 2010 Elsevier Inc. All rights reserved.