About this Journal Submit a Manuscript Table of Contents
Mediators of Inflammation
Volume 2010 (2010), Article ID 986596, 10 pages
http://dx.doi.org/10.1155/2010/986596
Review Article

Classification, Mechanisms of Action, and Therapeutic Applications of Inhibitory Oligonucleotides for Toll-Like Receptors (TLR) 7 and 9

Department of Internal Medicine, Division of Rheumatology, Carver College of Medicine, The University of Iowa, 200 Hawkins Drive, Iowa City, Iowa 52242, USA

Received 30 November 2009; Accepted 9 March 2010

Academic Editor: Philipp M. Lepper

Copyright © 2010 Petar S. Lenert. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Our immune defense depends on two specialized armed forces. The innate force acts as an alarm mechanism that senses changes in the microenvironment through the recognition of common microbial patterns by Toll-like receptors (TLR) and NOD proteins. It rapidly generates an inflammatory response aimed at neutralizing the intruder at the mucosal checkpoint. The innate arm also communicates this message with more specialized adaptive forces represented by pathogen-specific B cells and T cells. Interestingly, B cells also express some innate sensors, like TLR7 and TLR9, and may respond to bacterial hypomethylated CpG motifs and single-stranded RNA viruses. Intracellular nucleic acid sensing TLRs play an important role in the pathogenesis of Systemic Lupus Erythematosus (SLE). In this review, we describe recent achievements in the development of oligonucleotide—(ODN)-based inhibitors of TLR9 and/or TLR7 signaling. We categorize these novel therapeutics into Classes G, R, and B based on their cellular and molecular targets. Several short ODNs have already shown promise as pathway-specific therapeutics for animal lupus. We envision their future use in human SLE, microbial DNA-dependent sepsis, and in other autoinflammatory diseases.