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Critical Reviews™ in Immunology

ISSN for PRINT: 1040-8401

Institutional price:	$831.00
Issues per year:	6

Best Paper Award Selection - Editorial Board Site

2006, Volume26

111 pages

Issue price - $142.00

DNA Motifs Suppressing TLR9 Responses

Angela Trieu
Institute for Molecular Bioscience and CRC for Chronic Inflammatory Diseases, University of Queensland, Brisbane 4072, Australia

Tara L. Roberts
Institute for Molecular Bioscience and CRC for Chronic Inflammatory Diseases, University of Queensland, Brisbane 4072, Australia

Jasmyn A. Dunn
Institute for Molecular Bioscience and CRC for Chronic Inflammatory Diseases, University of Queensland, Brisbane 4072, Australia.

Matthew J. Sweet
Institute for Molecular Bioscience and CRC for Chronic Inflammatory Diseases, University of Queensland, Brisbane 4072, Australia

Katryn J. Stacey
Institute for Molecular Bioscience and CRC for Chronic Inflammatory Diseases, University of Queensland, Brisbane 4072, Australia

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 erythematosus (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 oligodeoxynucleotides (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.