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Nat Immunol. 2003 Jul;4(7):687-93. Epub 2003 May 25.

CpG directly induces T-bet expression and inhibits IgG1 and IgE switching in B cells.

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1
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

Abstract

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.

PMID:
12766768
DOI:
10.1038/ni941
[Indexed for MEDLINE]
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