Classification, mechanisms of action, and therapeutic applications of inhibitory oligonucleotides for Toll-like receptors (TLR) 7 and 9

Petar S Lenert

doi:10.1155/2010/986596

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Classification, mechanisms of action, and therapeutic applications of inhibitory oligonucleotides for Toll-like receptors (TLR) 7 and 9

Journal article

Open access

Peer reviewed

Classification, mechanisms of action, and therapeutic applications of inhibitory oligonucleotides for Toll-like receptors (TLR) 7 and 9

Petar S Lenert

Mediators of inflammation, Vol.2010, pp.986596-10

2010

DOI: 10.1155/2010/986596

PMCID: PMC2873634

PMID: 20490286

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https://doi.org/10.1155/2010/986596View

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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.

Animals

Base Sequence

CpG Islands

Humans

Lupus Erythematosus, Systemic - drug therapy

Oligonucleotides - classification

Oligonucleotides - metabolism

Oligonucleotides - therapeutic use

Telomere - genetics

Toll-Like Receptor 7 - antagonists & inhibitors

Toll-Like Receptor 7 - genetics

Toll-Like Receptor 7 - metabolism

Toll-Like Receptor 9 - antagonists & inhibitors

Toll-Like Receptor 9 - genetics

Toll-Like Receptor 9 - metabolism

Details

Title: Subtitle: Classification, mechanisms of action, and therapeutic applications of inhibitory oligonucleotides for Toll-like receptors (TLR) 7 and 9
Creators: Petar S Lenert - Roy J. and Lucille A. Carver College of Medicine
Resource Type: Journal article
Publication Details: Mediators of inflammation, Vol.2010, pp.986596-10
DOI: 10.1155/2010/986596
PMID: 20490286
PMCID: PMC2873634
NLM abbreviation: Mediators Inflamm
ISSN: 0962-9351
eISSN: 1466-1861
Grant note: R01 AI047374 / NIAID NIH HHS R56 AI064736 / NIAID NIH HHS AI047374 / NIAID NIH HHS AI064736 / NIAID NIH HHS
Language: English
Date published: 2010
Academic Unit: Immunology; Internal Medicine
Record Identifier: 9984359678802771

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