TLRs in the Gut. IV. Negative regulation of Toll-like receptors and intestinal homeostasis: Addition by subtraction

Oren Shibolet, Daniel K. Podolsky

Research output: Contribution to journalArticle

166 Citations (Scopus)

Abstract

Toll-like receptors (TLRs) are a family of transmembrane proteins that recognize conserved molecular motifs on microorganisms. Ligand binding to TLRs initiates signaling cascades that activate NF-κB, MAPK, and interferon response factors. These culminate in cellular responses including activation of antimicrobial killing mechanisms, production of cytokines and chemokines, maturation of antigen presenting cells, and the recruitment of the adaptive immune response. Intestinal epithelial cells represent a unique population of cells that exist in direct contact with a biomass of bacteria. Initiation of TLR signaling is tightly regulated because prolonged and excessive activation of TLRs can lead to uncontrolled inflammation detrimental to the host. Varied mechanisms appear to contribute to control of TLR activation in the intestinal epithelium. These include the collective effects of several negative regulators that include IRAK-M, TOLLIP, SIGIRR, A20, Nod2, and PPARγ. However, it remains to be determined whether they comprise the entire spectrum of negative control mechanisms and how they are bypassed to trigger activation during challenge by pathogens.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume292
Issue number6
DOIs
StatePublished - Jun 2007

Fingerprint

Toll-Like Receptors
Homeostasis
Peroxisome Proliferator-Activated Receptors
Adaptive Immunity
Antigen-Presenting Cells
Intestinal Mucosa
Chemokines
Biomass
Interferons
Epithelial Cells
Cytokines
Ligands
Inflammation
Bacteria
Population
Proteins

Keywords

  • Inflammation
  • Innate immunity
  • Ligand inhibition
  • Toll-like receptors

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology

Cite this

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