The glycoprotein-hormones activin A and inhibin A interfere with dendritic cell maturation.
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.
Segerer
Sabine E
SE
University of Würzburg, Department of Obstetrics and Gynecology, Josef-Schneider-Strasse 4, 97080 Würzburg, Germany. Engert_S1@klinik.uni-wuerzburg.de
Müller
Nora
N
Brandt
Jens van den
Jv
Kapp
Michaela
M
Dietl
Johannes
J
Reichardt
Holger M
HM
Rieger
Lorenz
L
Kämmerer
Ulrike
U
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
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