AI Article Synopsis
- Much of our current understanding of the innate immune response comes from non-physiological model systems, rather than actual immune cells.
- The study used a dual-tagging proteomic method to identify 16 potential MyD88-interacting partners in murine macrophages activated by lipid A, with Fliih confirmed as a key negative regulator of the TLR4-MyD88 signaling pathway.
- Fliih's reduction through small-interfering RNA enhanced NF-kappaB activation and cytokine production, indicating it plays a crucial role in regulating TLR pathway signaling.
Article 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-kappaB, 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.
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| http://dx.doi.org/10.4049/jimmunol.176.3.1355 | DOI Listing |
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