Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form
As of April 1st VIVO Scientific Profiles will no longer updated for faculty, and the link to VIVO will be removed from the library website. Faculty profile pages will continue to be updated via Interfolio. VIVO will continue being used behind the scenes to update graduate student profiles. Please contact helplib@scripps.edu if you have questions.
How to download citations from VIVO | Alternative profile options

Identification of a tlr4- and trif-dependent activation program of dendritic cells

Academic Article
uri icon
  • Overview
  • Research
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Weighardt, H.
  • Jusek, G.
  • Mages, J.
  • Lang, R.
  • Hoebe, K.
  • Beutler, Bruce
  • Holzmann, B.

publication date

  • February 2004

journal

  • European Journal of Immunology  Journal

abstract

  • Dendritic cell activation by Toll-like receptors (TLR) is crucial for the generation of protective immune responses. In addition to the common myeloid differentiation factor 88 (MyD88)-dependent signaling pathway, TLR4 engages the adaptor protein Toll/IL-1 receptor (TIR)-domain-containing adaptor inducing IFN-beta (TRIF), leading to interferon regulatory factor 3 (IRF-3) activation and type I interferon production. Using microarray expression profiling we now identify TRIF as a major regulator of the TLR4-triggered activation program of dendritic cells. We show that the expression of 47% of the genes that are responsive to TLR4 stimulation in wild-type dendritic cells is significantly altered in cells carrying a loss-of-function mutation of TRIF. Specifically, expression of IL-12, IL-18, and IL-23 was impaired in the absence of functional TRIF, suggesting that TLR4-promoted Th1 responses are TRIF-dependent. Furthermore, we provide evidence that TRIF regulates TLR4-mediated gene expression both by type I IFN-dependent and -independent mechanisms. Whereas dendritic cell production of CXCL10 and CCL12 was dependent on both TRIF and the type I interferon receptor, expression of IL-6 required TRIF but not type I interferon activity. Functional TRIF was also required for the normal induction of numerous genes considered important for host defense against diverse pathogens.Together, these data therefore identify TRIF as a crucial regulator of TLR4-dependent dendritic cell responses.

subject areas

  • Adaptor Proteins, Vesicular Transport
  • Animals
  • Cytokines
  • Dendritic Cells
  • Female
  • Gene Expression Regulation
  • Lipid A
  • Membrane Glycoproteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Oligonucleotide Array Sequence Analysis
  • RNA
  • Receptors, Cell Surface
  • Signal Transduction
  • Toll-Like Receptor 4
  • Toll-Like Receptors
scroll to property group menus

Research

keywords

  • dendritic cell
  • signal transduction
  • toll-like receptor
  • transcriptome analysis
scroll to property group menus

Identity

International Standard Serial Number (ISSN)

  • 0014-2980

Digital Object Identifier (DOI)

  • 10.1002/eji.200324714

PubMed ID

  • 14768061
scroll to property group menus

Additional Document Info

start page

  • 558

end page

  • 564

volume

  • 34

issue

  • 2

©2022 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support