title: The glycoprotein-hormones activin A and inhibin A interfere with dendritic cell maturation.
abstract: BACKGROUND
  Pregnancy represents an exclusive situation in which the immune and the endocrine system cooperate to prevent rejection of the embryo by the maternal immune system. While immature dendritic cells (iDC) in the early pregnancy decidua presumably contribute to the establishment of peripheral tolerance, glycoprotein-hormones of the transforming growth factor beta (TGF-beta) family including activin A (ActA) and inhibin A (InA) are candidates that could direct the differentiation of DCs into a tolerance-inducing phenotype.
  
  
  METHODS
  To test this hypothesis we generated iDCs from peripheral-blood-monocytes and exposed them to TGF-beta1, ActA, as well as InA and Dexamethasone (Dex) as controls.
  
  
  RESULTS
  Both glycoprotein-hormones prevented up-regulation of HLA-DR during cytokine-induced DC maturation similar to Dex but did not influence the expression of CD 40, CD 83 and CD 86. Visualization of the F-actin cytoskeleton confirmed that the DCs retained a partially immature phenotype under these conditions. The T-cell stimulatory capacity of DCs was reduced after ActA and InA exposure while the secretion of cytokines and chemokines was unaffected.
  
  
  CONCLUSIONS
  These findings suggest that ActA and InA interfere with selected aspects of DC maturation and may thereby help preventing activation of allogenic T-cells by the embryo. Thus, we have identified two novel members of the TGF-beta superfamily that could promote the generation of tolerance-inducing DCs.
authors.affiliation: University of Würzburg, Department of Obstetrics and Gynecology, Josef-Schneider-Strasse 4, 97080 Würzburg, Germany. Engert_S1@klinik.uni-wuerzburg.de
authors.forename: Sabine E
authors.initials: SE
authors.lastname: Segerer
authors.forename: Nora
authors.initials: N
authors.lastname: Müller
authors.forename: Jens van den
authors.initials: Jv
authors.lastname: Brandt
authors.forename: Michaela
authors.initials: M
authors.lastname: Kapp
authors.forename: Johannes
authors.initials: J
authors.lastname: Dietl
authors.forename: Holger M
authors.initials: HM
authors.lastname: Reichardt
authors.forename: Lorenz
authors.initials: L
authors.lastname: Rieger
authors.forename: Ulrike
authors.initials: U
authors.lastname: Kämmerer
mesh_terms: D000199:Actins / Q000032:analysis; D028341:Activins / Q000494:pharmacology / Q000502:physiology*; D000328:Adult; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D051940:B7-2 Antigen / Q000096:biosynthesis / Q000235:genetics; D019013:CD40 Antigens / Q000096:biosynthesis / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects / Q000648:ultrastructure; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology; D007136:Immunoglobulins / Q000096:biosynthesis / Q000235:genetics; D007265:Inhibins / Q000494:pharmacology / Q000502:physiology*; D053583:Interleukin-1beta / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D000097802:CD83 Antigen
chemical_list: D000199:Actins; D028341:Activins; D015703:Antigens, CD; D051940:B7-2 Antigen; D019013:CD40 Antigens; D003907:Dexamethasone; D006684:HLA-DR Antigens; D007136:Immunoglobulins; D007265:Inhibins; D053583:Interleukin-1beta; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D053773:Transforming Growth Factor beta1; D000097802:CD83 Antigen; C497964:CD86 protein, human; C508600:IL6 protein, human; C422405:activin A; C422362:inhibin A