Targeting Toll-like receptor signaling in plasmacytoid dendritic cells and autoreactive B cells as a therapy for lupus

Petar S Lenert

doi:10.1186/ar1888

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Targeting Toll-like receptor signaling in plasmacytoid dendritic cells and autoreactive B cells as a therapy for lupus

Journal article

Open access

Peer reviewed

Targeting Toll-like receptor signaling in plasmacytoid dendritic cells and autoreactive B cells as a therapy for lupus

Petar S Lenert

Arthritis research & therapy, Vol.8(1), pp.203-203

2006

DOI: 10.1186/ar1888

PMCID: PMC1526546

PMID: 16542467

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https://doi.org/10.1186/ar1888View

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Abstract

This review focuses on the role of Toll-like receptors (TLRs) in lupus and on possibilities to treat lupus using TLR modulating inhibitory oligodeoxynucleotides (INH-ODNs). TLRs bridge innate and adaptive immune responses and may play an important role in the pathogenesis of systemic lupus erythematosus. Of particular interest are TLR3, -7, -8, and -9, which are localized intracellularly. These TLRs recognize single-stranded or double-stranded RNA or hypomethylated CpG-DNA. Exposure to higher order CpG-DNA ligands or to immune complexed self-RNA triggers activation of autoreactive B cells and plasmacytoid dendritic cells. INH-ODNs were recently developed that block all downstream signaling events in TLR9-responsive cells. Some of these INH-ODNs can also target TLR7 signaling pathways. Based on their preferential cell reactivity, we classify INH-ODNs into class B and class R. Class B ('broadly reactive') INH-ODNs target a broad range of TLR-expressing cells. Class R ('restricted') INH-ODNs easily form DNA duplexes or higher order structures, and are preferentially recognized by autoreactive B cells and plasmacytoid dendritic cells, rather than by non-DNA specific follicular B cells. Both classes of INH-ODNs can block animal lupus. Hence, therapeutic application of these novel INH-ODNs in human lupus, particularly class R INH-ODNs, may result in more selective and disease-specific immunosuppression.

Autoimmunity

B-Lymphocytes - immunology

B-Lymphocytes - metabolism

Dendritic Cells - metabolism

Humans

Lupus Vulgaris - drug therapy

Oligonucleotides, Antisense - therapeutic use

Plasma Cells - metabolism

Signal Transduction

Toll-Like Receptors - genetics

Toll-Like Receptors - metabolism

Details

Title: Subtitle: Targeting Toll-like receptor signaling in plasmacytoid dendritic cells and autoreactive B cells as a therapy for lupus
Creators: Petar S Lenert - University of Iowa
Resource Type: Journal article
Publication Details: Arthritis research & therapy, Vol.8(1), pp.203-203
DOI: 10.1186/ar1888
PMID: 16542467
PMCID: PMC1526546
ISSN: 1478-6354
eISSN: 1478-6362
Grant note: R01 AI047374 / NIAID NIH HHS R01 AI 047374-01A2 / NIAID NIH HHS
Language: English
Date published: 2006
Academic Unit: Immunology; Internal Medicine
Record Identifier: 9984359702702771

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