CpG directly induces T-bet expression and inhibits IgG1 and IgE switching in B cells.
CpG DNA has immunomodulatory effects, such as the suppression of allergic responses mediated by type II T cell help (T(H)2). Here we report that CpG, but not lipopolysaccharide (LPS), rapidly induces expression of T-bet mRNA in purified B cells. Up-regulation of T-bet by CpG is abrogated in mice deficient in Toll-like receptor 9 (TLR9) and MyD88, but remains intact in B cells deficient in STAT1 (signal transducer and activator of transcription 1). Interleukin 12 (IL-12) alone does not up-regulate T-bet mRNA, but greatly enhances CpG-induced T-bet expression. Furthermore, CpG inhibits immunoglobulin G1 (IgG1) and IgE switching induced by IL-4 and CD40 signaling in purified B cells, and this effect correlates with up-regulation of T-bet. Thus, CpG triggers anti-allergic immune responses by directly regulating T-bet expression via a signaling pathway in B cells that is dependent upon TLR9, independent of interferon-gamma (IFN-gamma)-STAT1 and synergistic with IL-12.
Liu
Ningshu
N
Research Center Kyoto, Bayer Yakuhin Ltd., 6-5-1-3 Kunimidai, Kizu-cho, Soraku-gun, Kyoto 619-0216, Japan. ningshu.liu.nl@bayer.co.jp
Ohnishi
Noriko
N
Ni
Lin
L
Akira
Shizuo
S
Bacon
Kevin B
KB
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects*; D017578:Immunoglobulin Class Switching / Q000187:drug effects*; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000145:classification; D007371:Interferon-gamma / Q000502:physiology; D018664:Interleukin-12 / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D016328:NF-kappa B / Q000502:physiology; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000502:physiology; D011995:Recombination, Genetic; D050794:STAT1 Transcription Factor; D020825:T-Box Domain Proteins; D051217:Toll-Like Receptor 9; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D048051:p38 Mitogen-Activated Protein Kinases; D000098815:T-bet Transcription Factor
C408982:CPG-oligonucleotide; D004268:DNA-Binding Proteins; D007074:Immunoglobulin G; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D011956:Receptors, Cell Surface; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D015534:Trans-Activators; D014157:Transcription Factors; D018664:Interleukin-12; D007073:Immunoglobulin E; D007371:Interferon-gamma; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases