通過漿細胞樣樹突狀細胞(pDCs)的異常激發(fā)來產(chǎn)生干擾素,會引起由免疫系統(tǒng)調控的炎癥和牛皮癬的發(fā)病?,F(xiàn)在,,這一效應的一個誘因已被識別出來,其形式為人抗菌肽LL37,,后者見于牛皮癬患者的皮膚中和受損的皮膚中,。這種肽也被稱為CAMP,它能將由正在死亡的細胞釋放的本來是非刺激性的self-DNA轉化成pDCs中干擾素生產(chǎn)的一種強效激發(fā)因子,。這些發(fā)現(xiàn)為LL-37過度表達在驅動牛皮癬以及其他相關疾病中的自免疫皮膚炎癥中可能發(fā)揮一定作用的觀點提供了證據(jù),。因此,LL-37拮抗藥物對于治療炎癥可能是有效的,,而且LL-37本身也可能是疫苗的一種有用的輔藥,。
原始出處:
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: [email protected]).
Abstract
兩種藥對牛皮癬療效獲證實
牛皮癬可能出現(xiàn)淋巴瘤高發(fā)危險
一種新藥將用于治療牛皮癬
英國研究發(fā)現(xiàn)牛皮癬與基因有關
PLoS ONE:造成牛皮癬等皮膚病的microRNA分子
硫鳥嘌呤能夠清除頑固性牛皮癬
美國研究人員識別出3個與牛皮癬發(fā)病相關基因
ENBREL在劑量減少后為牛皮癬患者帶來持續(xù)療效
基因與牛皮癬
牛皮癬:皮膚癥狀或許只是冰山一角
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.