Antimicrobial peptides and self-DNA in autoimmune skin inflammation.
Toll-like receptor (TLR)-mediated detection of viral nucleic acids and production of type I interferons (IFNs) by plasmacytoid dendritic cells (pDCs) are key elements of antiviral defense. By contrast, inappropriate recognition of self-nucleic acids with induction of IFN responses in pDCs can lead to autoimmunity. In this review we describe how pDC responses to self-DNA are normally avoided and focus on our recent finding that in psoriasis, a common autoimmune disease of the skin, these barriers can be breached by the cationic antimicrobial peptide LL37. LL37 binds extracellular self-DNA fragments into aggregated particles that enter pDCs and trigger robust IFN responses by activating endosomal TLR9 as if they were viruses. We also describe the mechanisms that normally control production and activity of LL37 in human skin and propose that the persistent overexpression of LL37 in psoriasis leads to uncontrolled IFN responses that drive autoimmune skin inflammation.
Gilliet
Michel
M
Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. mgilliet@mdanderson.org
Lande
Roberto
R
D023181:Antimicrobial Cationic Peptides / Q000276:immunology / Q000378:metabolism*; D001327:Autoimmune Diseases / Q000276:immunology* / Q000378:metabolism; D015551:Autoimmunity; D054804:Cathelicidins; D004247:DNA / Q000276:immunology* / Q000378:metabolism; D004279:DNA, Viral / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D003855:Deoxyribose / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D007370:Interferon Type I / Q000276:immunology / Q000378:metabolism*; D011565:Psoriasis / Q000276:immunology* / Q000378:metabolism; D017634:Self Tolerance; D012867:Skin / Q000276:immunology / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000276:immunology / Q000378:metabolism*
D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D004279:DNA, Viral; D007370:Interferon Type I; D051217:Toll-Like Receptor 9; D003855:Deoxyribose; D004247:DNA