Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide.

Abstract:

: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.

journal_name

Nature

journal_title

Nature

authors

Lande R,Gregorio J,Facchinetti V,Chatterjee B,Wang YH,Homey B,Cao W,Wang YH,Su B,Nestle FO,Zal T,Mellman I,Schröder JM,Liu YJ,Gilliet M

doi

10.1038/nature06116

subject

Has Abstract

pub_date

2007-10-04 00:00:00

pages

564-9

issue

7162

eissn

0028-0836

issn

1476-4687

pii

nature06116

journal_volume

449

pub_type

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