Flightless I homolog negatively modulates the TLR pathway

Tianyi Wang, Tsung Hsien Chuang, Tapani Ronni, Sheng Gu, Yu Chun Du, Hong Cai, Hui Qiao Sun, Helen L. Yin, Xian Chen

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

To date, much of our knowledge about the signaling networks involved in the innate immune response has come from studies using nonphysiologic model systems rather than actual immune cells. In this study, we used a dual-tagging proteomic strategy to identify the components of the MyD88 signalosome in murine macrophages stimulated with lipid A. This systems approach revealed 16 potential MyD88-interacting partners, one of which, flightless I homolog (Fliih) was verified to interact with MyD88 and was further characterized as a negative regulator of the TLR4-MyD88 pathway. Conversely, a reduction in endogenous Fliih by small-interfering RNA enhanced the activation of NF-κB, as well as cytokine production by LPS. Results from immunoprecipitation and a two-hybrid assay further indicated that Fliih directly interfered with the formation of the TLR4-MyD88 signaling complex. These results in turn suggest a new basis for the regulation of the TLR pathway by Fliih.

Original languageEnglish (US)
Pages (from-to)1355-1362
Number of pages8
JournalJournal of Immunology
Volume176
Issue number3
DOIs
StatePublished - Feb 1 2006

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Wang, T., Chuang, T. H., Ronni, T., Gu, S., Du, Y. C., Cai, H., Sun, H. Q., Yin, H. L., & Chen, X. (2006). Flightless I homolog negatively modulates the TLR pathway. Journal of Immunology, 176(3), 1355-1362. https://doi.org/10.4049/jimmunol.176.3.1355