title: Ursodeoxycholic acid suppresses eosinophilic airway inflammation by inhibiting the function of dendritic cells through the nuclear farnesoid X receptor.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratory of Immunoregulation and Mucosal Immunology, Department of Molecular Biomedical Research, Flemish Interuniversity Institute of Biotechnology, Ghent, Belgium.
authors.forename: M A M
authors.initials: MA
authors.lastname: Willart
authors.forename: M
authors.initials: M
authors.lastname: van Nimwegen
authors.forename: A
authors.initials: A
authors.lastname: Grefhorst
authors.forename: H
authors.initials: H
authors.lastname: Hammad
authors.forename: L
authors.initials: L
authors.lastname: Moons
authors.forename: H C
authors.initials: HC
authors.lastname: Hoogsteden
authors.forename: B N
authors.initials: BN
authors.lastname: Lambrecht
authors.forename: A
authors.initials: A
authors.lastname: Kleinjan
mesh_terms: D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D002450:Cell Communication / Q000187:drug effects / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology*; D005260:Female; D007155:Immunologic Factors / Q000008:administration & dosage / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011657:Pulmonary Eosinophilia / Q000188:drug therapy* / Q000276:immunology; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D016207:Cytokines; D007155:Immunologic Factors; D018160:Receptors, Cytoplasmic and Nuclear; D014580:Ursodeoxycholic Acid; D000099150:Receptor, Farnesoid X-Activated