Format

Send to

Choose Destination
Cell Immunol. 2019 Apr;338:1-8. doi: 10.1016/j.cellimm.2019.02.006. Epub 2019 Feb 22.

The TLR7 agonist imiquimod selectively inhibits IL-4-induced IgE production by suppressing IgG1/IgE class switching and germline ε transcription through the induction of BCL6 expression in B cells.

Author information

1
Department of Microbiology, Myunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon 35365, Republic of Korea.
2
Department of Molecular Bioscience, School of Biomedical Science, Kangwon National University, Chuncheon 24341, Republic of Korea.
3
Department of Microbiology, Myunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon 35365, Republic of Korea; Priority Research Center, Myunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon 35365, Republic of Korea. Electronic address: srpark@konyang.ac.kr.

Abstract

Imiquimod (IMQ) is a selective toll-like receptor 7 (TLR7) agonist. TLR7 activation leads to the production of IFN-γ and pro-inflammatory cytokines by innate immune cells. However, the role of TLR7 in B cells is not fully understood. In this study, we investigated the direct effect of in vitro stimulation with IMQ on Ab production and isotype switching in B cells. IMQ selectively diminished IL-4-induced IgE and IgG1 production in anti-CD40-activated mouse B cells. IMQ also inhibited germline ε transcripts (GLTε)/GLTγ1 and post-switch ε transcripts (PSTε)/PSTγ1 expression, while enhancing GLTγ2c and PSTγ2c expression in anti-CD40/IL-4-stimulated B cells. Interestingly, IMQ abrogated IL-4-induced circle transcripts ε-γ1 (CTε-γ1) expression, indicative of sequential switching from IgG1 to IgE. Furthermore, IMQ repressed IL-4-induced surface IgE/IgG1 expression while increasing surface IgG2c expression. The selective inhibition of IgE synthesis was not due to IMQ-induced production of IFN-γ or IL-12 in the same culture. IMQ also enhanced BCL6 expression, a transcriptional repressor for the GLTε promoter, in anti-CD40/IL-4-stimulated B cells. In addition, BCL6 siRNA restored IMQ-mediated suppression of GLTε transcription. Therefore, these results indicate that TLR7 engagement by IMQ inhibits IL-4-induced GLTε transcription by enhancing BCL6 expression and inhibits IL-4-induced sequential switching from IgM to IgE via IgG1, thus resulting in the downregulation of IgE production by B cells.

KEYWORDS:

B cells; BCL6; Germline ε transcripts; IgE; Imiquimod; TLR7

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center