Rabbit Anti-Human TLR13 Polyclonal antibody

Psoriasis is an inflammatory skin disease with strong neutrophil (PMN) infiltration and high levels of the antimicrobial peptide, LL37. LL37 in complex with DNA and RNA is thought to initiate disease exacerbation via plasmacytoid dendritic cells. However, the source of nucleic acids supposed to start this initial inflammatory event remains unknown. We show here that primary murine and human PMNs mount a fulminant and self-propagating neutrophil extracellular trap (NET) and cytokine response, but independently of the canonical NET component, DNA. Unexpectedly, RNA, which is abundant in NETs and psoriatic but not healthy skin, in complex with LL37 triggered TLR8/TLR13-mediated cytokine and NET release by PMNs in vitro and in vivo. Transfer of NETs to naive human PMNs prompts additional NET release, promoting further inflammation. Our study thus uncovers a self-propagating vicious cycle contributing to chronic inflammation in psoriasis, and NET-associated RNA (naRNA) as a physiologically relevant NET component.

Pathogen sensors such as Toll-like receptors (TLRs) detect microorganism- or host-derived conserved molecular structures, including lipids or nucleic acids and provoke activation of Ag presenting cells such as dendritic cells (DCs). Several synthetic TLR ligands, especially oligonucleotides, are being developed as promising vaccines for infectious diseases, cancers or allergies. DCs are heterogeneous and consist of various subsets, each of which expresses a subset-specific repertoire of TLRs and responds to the TLR signaling in a subset-specific manner. Furthermore, each DC subset expresses a set of chemokine receptors that regulate its function and behavior. Here I review the functions of two DC subsets and how chemokine receptors function in these subsets. One is the plasmacytoid DC (pDC), which expresses nucleic acid sensing receptors TLR7 and TLR9 and secretes large amounts of type I interferons in response to TLR7/9 signaling. The other is splenic CD8 alpha(+) conventional DC (cDC). This DC subset expresses lipid sensors, TLR2 and TLR4, and nucleic acid sensors, TLR3, TLR9 and TLR13 and is specialized for antigen crosspresentation. Several chemokine receptors are differentially expressed on these DC subsets. The homologues of these murine DC subsets are also found in humans. Understanding how these DC subsets function and respond to TLR ligands and chemokines should be important for development of effective vaccines. (C) 2012 Elsevier Ltd. All rights reserved.