RESEARCH - Antimicrobial peptides and self-DNA in autoimmune skin inflammation

[Guest guest]

Curr Opin Immunol. 2008 Jul 5.

Antimicrobial peptides and self-DNA in autoimmune skin inflammation.

Gilliet M, Lande R.

Department of Immunology, The University of Texas M.D. Cancer

Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA; Department of

Melanoma Medical Oncology, The University of Texas M.D.

Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.

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. On the other

contrary, 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 IFN responses that drive

autoimmune skin inflammation.

PMID: 18611439

http://www.ncbi.nlm.nih.gov/pubmed/18611439

--

Not an MD