Nature：牛皮癣的一个诱因
通过浆细胞样树突状细胞（pDCs）的异常激发来产生干扰素，会引起由免疫系统调控的炎症和牛皮癣的发病。现在，这一效应的一个诱因已被识别出来，其形式为人抗菌肽LL37，后者见于牛皮癣患者的皮肤中和受损的皮肤中。这种肽也被称为CAMP，它能将由正在死亡的细胞释放的本来是非刺激性的self-DNA转化成pDCs中干扰素生产的一种强效激发因子。这些发现为LL-37过度表达在驱动牛皮癣以及其他相关疾病中的自免疫皮肤炎症中可能发挥一定作用的观点提供了证据。因此，LL-37拮抗药物对于治疗炎症可能是有效的，而且LL-37本身也可能是疫苗的一种有用的辅药。
原始出处:
Nature 449, 564-569 (4 October 2007) | doi:10.1038/nature06116; Received 19 April 2007; Accepted 26 July 2007; Published online 16 September 2007
Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide
Roberto Lande1, Josh Gregorio1, Valeria Facchinetti1, Bithi Chatterjee3,4, Yi-Hong Wang1, Bernhard Homey5, Wei Cao1, Yui-Hsi Wang1, Bing Su1, Frank O. Nestle6, Tomasz Zal1, Ira Mellman3,4, Jens-Michael Schröder7, Yong-Jun Liu1 & Michel Gilliet1,2
- Department of Immunology, and,
- Department of Melanoma Medical Oncology, M. D. Anderson Cancer Center, University of Texas, Houston, Texas 77030, USA
- Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06520-8002, USA
- Genentech., 1 DNA Way, South San Francisco, California 94080, USA
- Department of Dermatology, Heinrich-Heine-University, Düsseldorf 40225, Germany
- St John's Institute of Dermatology, King's College London School of Medicine, London SE1 9RT, UK
- Department of Dermatology, University Hospital Schleswig-Holstein, Campus Kiel, University of Kiel, Kiel 24105, Germany
Correspondence to: Michel Gilliet1,2 Correspondence and requests for materials should be addressed to M.G. (Email: mgilliet@mdanderson.org).
Abstract
| PLoS ONE：造成牛皮癣等皮肤病的microRNA分子 |
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.
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