Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide
Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide
复制标题
DOI：
10.1038/nature06116
复制
发表时间：
2007-10-04
期刊：
影响因子：
64.8
通讯作者：
Gilliet, Michel
中科院分区：
文献类型：
--
作者：
Lande, Roberto;Gregorio, Josh;Gilliet, Michel
浆细胞样树突状细胞 (pDC) 通过内体 Toll 样受体感知病毒和微生物 DNA，从而产生 1 型干扰素。 pDC 通常不会对自身 DNA 做出反应，但在人类自身免疫性疾病中，这种限制似乎通过一种尚不清楚的机制被打破。在这里，我们将抗菌肽 LL37（也称为 CAMP）确定为介导银屑病（一种常见的自身免疫性皮肤病）中 pDC 激活的关键因子。 LL37 通过结合 DNA 形成聚集和浓缩的结构，将惰性自身 DNA 转化为干扰素产生的有效触发因素，这些结构被递送到并保留在 pDC 的早期内吞区室中，以触发 Toll 样受体 9。因此，我们的数据揭示了内源性抗菌肽在打破对自身 DNA 的先天耐受性方面的基本作用，并表明该途径可能驱动 牛皮癣的自身免疫。
Plasmacytoid dendritic cells (pDCs) sense viral and microbial DNA through endosomal Toll-like receptors to produce type 1 interferons. pDCs do not normally respond to self-DNA, but this restriction seems to break down in human autoimmune disease by an as yet poorly understood mechanism. Here we identify the antimicrobial peptide LL37 (also known as CAMP) as the key factor that mediates pDC activation in psoriasis, a common autoimmune disease of the skin. LL37 converts inert self-DNA into a potent trigger of interferon production by binding the DNA to form aggregated and condensed structures that are delivered to and retained within early endocytic compartments in pDCs to trigger Toll-like receptor 9. Thus, our data uncover a fundamental role of an endogenous antimicrobial peptide in breaking innate tolerance to self-DNA and suggest that this pathway may drive autoimmunity in psoriasis.