title: 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.
authors.affiliation: Department of Immunology, M. D. Anderson Cancer Center, University of Texas, Houston, Texas 77030, USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Lande
authors.forename: Josh
authors.initials: J
authors.lastname: Gregorio
authors.forename: Valeria
authors.initials: V
authors.lastname: Facchinetti
authors.forename: Bithi
authors.initials: B
authors.lastname: Chatterjee
authors.forename: Yi-Hong
authors.initials: YH
authors.lastname: Wang
authors.forename: Bernhard
authors.initials: B
authors.lastname: Homey
authors.forename: Wei
authors.initials: W
authors.lastname: Cao
authors.forename: Yui-Hsi
authors.initials: YH
authors.lastname: Wang
authors.forename: Bing
authors.initials: B
authors.lastname: Su
authors.forename: Frank O
authors.initials: FO
authors.lastname: Nestle
authors.forename: Tomasz
authors.initials: T
authors.lastname: Zal
authors.forename: Ira
authors.initials: I
authors.lastname: Mellman
authors.forename: Jens-Michael
authors.initials: JM
authors.lastname: Schröder
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Liu
authors.forename: Michel
authors.initials: M
authors.lastname: Gilliet
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000378:metabolism*; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism*; D001327:Autoimmune Diseases / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015551:Autoimmunity; D054804:Cathelicidins; D004247:DNA / Q000276:immunology / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D004705:Endocytosis; D011992:Endosomes / Q000276:immunology / Q000378:metabolism; D006801:Humans; D011565:Psoriasis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051217:Toll-Like Receptor 9 / Q000276:immunology / Q000378:metabolism
chemical_list: D023181:Antimicrobial Cationic Peptides; D001324:Autoantigens; D054804:Cathelicidins; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D004247:DNA