The glycoprotein-hormones activin A and inhibin A interfere with dendritic cell maturation

Sabine E Segerer¹ , Nora Müller² , Jens van den Brandt³ , Michaela Kapp¹ , Johannes Dietl¹ , Holger M Reichardt²^,3 , Lorenz Rieger¹ and Ulrike Kämmerer¹

¹University of Würzburg, Department of Obstetrics and Gynecology, Josef-Schneider-Straße 4, 97080 Würzburg, Germany

²University of Würzburg, Institute for Virology and Immunobiology, Versbacherstraße 7, 97078 Würzburg, Germany

³University of Göttingen, Medical School, Department of Cellular and Molecular Immunology, Humboldtallee 34, 37073 Göttingen, Germany

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Reproductive Biology and Endocrinology 2008, 6:17doi:10.1186/1477-7827-6-17


Published:	6 May 2008

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.

Conclusion

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.