Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0054472
Title: The Bile Acid Sensor FXR Is Required for Immune-Regulatory Activities of TLR-9 in Intestinal Inflammation
Authors: Renga B.
Mencarelli A. 
Cipriani S.
D'Amore C.
Carino A.
Bruno A.
Francisci D.
Zampella A.
Distrutti E.
Fiorucci S.
Keywords: farnesoid X receptor
interferon regulatory factor 7
myeloid differentiation factor 88
toll like receptor 2
toll like receptor 3
toll like receptor 4
toll like receptor 5
toll like receptor 6
toll like receptor 7
toll like receptor 8
toll like receptor 9
tumor necrosis factor alpha
animal cell
animal experiment
animal model
animal tissue
article
cell activation
controlled study
enteritis
farnesoid X receptor gene
gene expression
human
human cell
immune response
immunoregulation
male
mouse
nonhuman
promoter region
protein expression
protein function
protein protein interaction
receptor upregulation
signal transduction
Animals
Cells, Cultured
Colitis
Gene Expression Regulation
Humans
Immunity, Innate
Inflammation
Interferon Regulatory Factor-7
Intestines
Male
Mice
Mice, Knockout
Monocytes
Myeloid Differentiation Factor 88
Oligodeoxyribonucleotides
Promoter Regions, Genetic
Receptors, Cytoplasmic and Nuclear
Signal Transduction
Toll-Like Receptor 9
Trinitrobenzenesulfonic Acid
Tumor Necrosis Factor-alpha
Mus
Issue Date: 2013
Citation: Renga B., Mencarelli A., Cipriani S., D'Amore C., Carino A., Bruno A., Francisci D., Zampella A., Distrutti E., Fiorucci S. (2013). The Bile Acid Sensor FXR Is Required for Immune-Regulatory Activities of TLR-9 in Intestinal Inflammation. PLoS ONE 8 (1) : e54472. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0054472
Rights: Attribution 4.0 International
Abstract: Background: Toll like receptors (TLRs) sense the intestinal microbiota and regulate the innate immune response. A dysregulation of TLRs function participates into intestinal inflammation. Farnesoid X Receptor (FXR) is a nuclear receptor and bile acid sensor highly expressed in entero-hepatic tissues. FXR regulates lipid metabolism and innate immunity. Methodology/Principal Findings: In this study we have investigated whether FXR gene expression/function in the intestine is modulated by TLRs. We found that in human monocytes activation of membrane TLRs (i.e. TLR2, 4, 5 and 6) downregulates, while activation of intracellular TLRs (i.e. TLR3, 7, 8 and 9) upregulates the expression of FXR and its target gene SHP, small heterodimer partner. This effect was TLR9-dependent and TNF? independent. Intestinal inflammation induced in mice by TNBS downregulates the intestinal expression of FXR in a TLR9-dependent manner. Protection against TNBS colitis by CpG, a TLR-9 ligand, was lost in FXR-/- mice. In contrast, activation of FXR rescued TLR9-/- and MyD88-/- mice from colitis. A putative IRF7 response element was detected in the FXR promoter and its functional characterization revealed that IRF7 is recruited on the FXR promoter under TLR9 stimulation. Conclusions/Significance: Intestinal expression of FXR is selectively modulated by TLR9. In addition to its role in regulating type-I interferons and innate antiviral immunity, IRF-7 a TLR9-dependent factor, regulates the expression of FXR, linking microbiota-sensing receptors to host's immune and metabolic signaling. © 2013 Renga et al.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/161348
ISSN: 19326203
DOI: 10.1371/journal.pone.0054472
Rights: Attribution 4.0 International
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