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Ursodeoxycholic acid suppresses eosinophilic airway inflammation by inhibiting the function of dendritic cells through the nuclear farnesoid X receptor

Monique Willart, M van Nimwegen, A Grefhorst, Hamida Hammad UGent, L Moons, HC Hoogsteden, Bart Lambrecht UGent and A KleinJan (2012) ALLERGY. 67(12). p.1501-1510
abstract
Background : Ursodeoxycholic acid (UDCA) is the only known beneficial bile acid with immunomodulatory properties. Ursodeoxycholic acid prevents eosinophilic degranulation and reduces eosinophil counts in primary biliary cirrhosis. It is unknown whether UDCA would also modulate eosinophilic inflammation outside the gastrointestinal (GI) tract, such as eosinophilic airway inflammation seen in asthma. The working mechanism for its immunomodulatory effect is unknown. Methods : The immunosuppressive features of UDCA were studied in vivo, in mice, in an ovalbumin (OVA)-driven eosinophilic airway inflammation model. To study the mechanism of action of UDCA, we analyzed the effect of UDCA on eosinophils, T cells, and dendritic cell (DCs). DC function was studied in greater detail, focussing on migration and T-cell stimulatory strength in vivo and interaction with T cells in vitro as measured by time-lapse image analysis. Finally, we studied the capacity of UDCA to influence DC/T cell interaction. Results : Ursodeoxycholic acid treatment of OVA-sensitized mice prior to OVA aerosol challenge significantly reduced eosinophilic airway inflammation compared with control animals. DCs expressed the farnesoid X receptor for UDCA. Ursodeoxycholic acid strongly promoted interleukin (IL)-12 production and enhanced the migration in DCs. The time of interaction between DCs and T cells was sharply reduced in vitro by UDCA treatment of the DCs resulting in a remarkable T-cell cytokine production. Ursodeoxycholic acid-treated DCs have less capacity than saline-treated DCs to induce eosinophilic inflammation in vivo in Balb/c mice. Conclusion : Ursodeoxycholic acid has the potency to suppress eosinophilic inflammation outside the GI tract. This potential comprises to alter critical function of DCs, in essence, the effect of UDCA on DCs through the modulation of the DC/T cell interaction.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
DEGRANULATION, ASTHMA, KAPPA-B, TH2 RESPONSES, ADAPTIVE IMMUNITY, MOUSE MODEL, INHALED ANTIGEN, BILE-ACIDS, PHOSPHOLIPASE A(2) EXPRESSION, PRIMARY BILIARY-CIRRHOSIS, ursodeoxycholic acid, gastrointestinal tract, farnesoid X receptor, eosinophilic airway inflammation, dendritic cell
journal title
ALLERGY
Allergy
volume
67
issue
12
pages
1501 - 1510
Web of Science type
Article
Web of Science id
000311055100005
JCR category
ALLERGY
JCR impact factor
5.883 (2012)
JCR rank
2/23 (2012)
JCR quartile
1 (2012)
ISSN
0105-4538
DOI
10.1111/all.12019
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
3077242
handle
http://hdl.handle.net/1854/LU-3077242
date created
2012-12-20 15:15:56
date last changed
2016-12-19 15:39:04
@article{3077242,
  abstract     = {Background : Ursodeoxycholic acid (UDCA) is the only known beneficial bile acid with immunomodulatory properties. Ursodeoxycholic acid prevents eosinophilic degranulation and reduces eosinophil counts in primary biliary cirrhosis. It is unknown whether UDCA would also modulate eosinophilic inflammation outside the gastrointestinal (GI) tract, such as eosinophilic airway inflammation seen in asthma. The working mechanism for its immunomodulatory effect is unknown. 
Methods : The immunosuppressive features of UDCA were studied in vivo, in mice, in an ovalbumin (OVA)-driven eosinophilic airway inflammation model. To study the mechanism of action of UDCA, we analyzed the effect of UDCA on eosinophils, T cells, and dendritic cell (DCs). DC function was studied in greater detail, focussing on migration and T-cell stimulatory strength in vivo and interaction with T cells in vitro as measured by time-lapse image analysis. Finally, we studied the capacity of UDCA to influence DC/T cell interaction. 
Results : Ursodeoxycholic acid treatment of OVA-sensitized mice prior to OVA aerosol challenge significantly reduced eosinophilic airway inflammation compared with control animals. DCs expressed the farnesoid X receptor for UDCA. Ursodeoxycholic acid strongly promoted interleukin (IL)-12 production and enhanced the migration in DCs. The time of interaction between DCs and T cells was sharply reduced in vitro by UDCA treatment of the DCs resulting in a remarkable T-cell cytokine production. Ursodeoxycholic acid-treated DCs have less capacity than saline-treated DCs to induce eosinophilic inflammation in vivo in Balb/c mice. 
Conclusion : Ursodeoxycholic acid has the potency to suppress eosinophilic inflammation outside the GI tract. This potential comprises to alter critical function of DCs, in essence, the effect of UDCA on DCs through the modulation of the DC/T cell interaction.},
  author       = {Willart, Monique and van Nimwegen, M and Grefhorst, A and Hammad, Hamida and Moons, L and Hoogsteden, HC and Lambrecht, Bart and KleinJan, A},
  issn         = {0105-4538},
  journal      = {ALLERGY},
  keyword      = {DEGRANULATION,ASTHMA,KAPPA-B,TH2 RESPONSES,ADAPTIVE IMMUNITY,MOUSE MODEL,INHALED ANTIGEN,BILE-ACIDS,PHOSPHOLIPASE A(2) EXPRESSION,PRIMARY BILIARY-CIRRHOSIS,ursodeoxycholic acid,gastrointestinal tract,farnesoid X receptor,eosinophilic airway inflammation,dendritic cell},
  language     = {eng},
  number       = {12},
  pages        = {1501--1510},
  title        = {Ursodeoxycholic acid suppresses eosinophilic airway inflammation by inhibiting the function of dendritic cells through the nuclear farnesoid X receptor},
  url          = {http://dx.doi.org/10.1111/all.12019},
  volume       = {67},
  year         = {2012},
}

Chicago
Willart, Monique, M van Nimwegen, A Grefhorst, Hamida Hammad, L Moons, HC Hoogsteden, Bart Lambrecht, and A KleinJan. 2012. “Ursodeoxycholic Acid Suppresses Eosinophilic Airway Inflammation by Inhibiting the Function of Dendritic Cells Through the Nuclear Farnesoid X Receptor.” Allergy 67 (12): 1501–1510.
APA
Willart, M., van Nimwegen, M., Grefhorst, A., Hammad, H., Moons, L., Hoogsteden, H., Lambrecht, B., et al. (2012). Ursodeoxycholic acid suppresses eosinophilic airway inflammation by inhibiting the function of dendritic cells through the nuclear farnesoid X receptor. ALLERGY, 67(12), 1501–1510.
Vancouver
1.
Willart M, van Nimwegen M, Grefhorst A, Hammad H, Moons L, Hoogsteden H, et al. Ursodeoxycholic acid suppresses eosinophilic airway inflammation by inhibiting the function of dendritic cells through the nuclear farnesoid X receptor. ALLERGY. 2012;67(12):1501–10.
MLA
Willart, Monique, M van Nimwegen, A Grefhorst, et al. “Ursodeoxycholic Acid Suppresses Eosinophilic Airway Inflammation by Inhibiting the Function of Dendritic Cells Through the Nuclear Farnesoid X Receptor.” ALLERGY 67.12 (2012): 1501–1510. Print.