DNA Motifs Suppressing TLR9 Responses

Trieu, A., Roberts, T. L., Dunn, J. A., Sweet, M. J. and Stacey, K. J. (2006) DNA Motifs Suppressing TLR9 Responses. Critical reviews in Immunology, 26 6: 527-544. doi:10.1615/CritRevImmunol.v26.i6.50

Author Trieu, A.
Roberts, T. L.
Dunn, J. A.
Sweet, M. J.
Stacey, K. J.
Title DNA Motifs Suppressing TLR9 Responses
Journal name Critical reviews in Immunology   Check publisher's open access policy
ISSN 1040-8401
Publication date 2006-01-01
Year available 2006
Sub-type Article (original research)
DOI 10.1615/CritRevImmunol.v26.i6.50
Open Access Status Not yet assessed
Volume 26
Issue 6
Start page 527
End page 544
Total pages 18
Place of publication Redding CT USA
Publisher Begell House Inc
Language eng
Subject C1
320202 Cellular Immunology
730101 Infectious diseases
Abstract Immune cells respond to bacterial DNA containing unmethylated CpG motifs via Toll-like receptor 9 (TLR9). Given the apparent role of TLR9 in development of systemic lupus erythernatosus (SLE), there is interest in the development of TLR9 inhibitors. TLR9-mediated responses are reported to be inhibited by a confusing variety of different DNA sequences and structures. To aid characterization, we have provisionally categorized TLR9-inhibitory oligodeoxynucleoti des (ODN) into 4 classes, on the basis of sequence and probable mode of action. Class I are short G-rich ODN, which show sequence-specific inhibition of all TLR9 responses, and may be direct competitive inhibitors for DNA binding to TLR9. Class II are telomeric repeat motifs that inhibit STAT signaling, and thus are not specific to TLR9 responses. Because Class II ODN are generally made as 24-base phosphorothioate-modified ODN (PS-ODN), they also fall into Class IV, defined as long PS-ODN, which inhibit TLR9 responses in a sequence-nonspecific manner. Class III includes oligo (dG) that forms a 4-stranded structure and inhibits DNA uptake. The Class I G-rich motifs show the most promise as selective and potent TLR9 inhibitors for therapeutic applications.
Keyword Immunology
systemic lupus erythematosus
immunosuppressive DNA motifs
Induced Immune Activation
Toll-like Receptors
Stimulatory Cpg Oligonucleotides
Plasmacytoid Dendritic Cells
Ifn-alpha Production
I Interferon System
Murine Lupus
Q-Index Code C1
Institutional Status UQ

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Created: Wed, 15 Aug 2007, 20:53:23 EST