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

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p

The glycoprotein-hormones activin A and inhibin A interfere with dendritic cell maturation-2

Ce of the four hormones was analyzed by cytokine bead array for the production of IL-8, IL-10, MCP-1 and RANTES. Mean +/- SEM, n = 7- 8; ** p < 0,01 (hormonal treatment vs. mDC).<p><b>Copyright information:</b></p><p>Taken from "The glycoprotein-hormones activin A and inhibin A interfere with dendritic cell maturation"</p><p>http://www.rbej.com/content/6/1/17</p><p>Reproductive biology and endocrinology : RB&E 2008;6():17-17.</p><p>Published online 6 May 2008</p><p>PMCID:PMC2412882.</p><p></p

The glycoprotein-hormones activin A and inhibin A interfere with dendritic cell maturation-0

Th IL-4 and GM-CSF. Differentiation into mature DCs (mDCs) was achieved by addition of an inflammatory cytokine cocktail for 24 hours. To study the impact of various hormones on the maturation process, maturation was performed in the presence or absence of Dex, TGF-β1, ActA or InA. Subsequently, the cells were analyzed for surface expression of CD40, CD83, CD86 and HLA-DR by flow cytometry. Representative histograms (left panel) are depicted for each hormonal treatment (grey shaded areas); analysis of corresponding iDCs (grey line) and mDCs (black line) are shown in each histogram for control. In addition, statistical analysis of the mean fluorescence intensity (MFI) as a quantitative measure for surface expression levels is depicted as bar diagrams (right panel). n = 14.<p><b>Copyright information:</b></p><p>Taken from "The glycoprotein-hormones activin A and inhibin A interfere with dendritic cell maturation"</p><p>http://www.rbej.com/content/6/1/17</p><p>Reproductive biology and endocrinology : RB&E 2008;6():17-17.</p><p>Published online 6 May 2008</p><p>PMCID:PMC2412882.</p><p></p

The glycoprotein-hormones activin A and inhibin A interfere with dendritic cell maturation-4

Th IL-4 and GM-CSF. Differentiation into mature DCs (mDCs) was achieved by addition of an inflammatory cytokine cocktail for 24 hours. To study the impact of various hormones on the maturation process, maturation was performed in the presence or absence of Dex, TGF-β1, ActA or InA. Subsequently, the cells were analyzed for surface expression of CD40, CD83, CD86 and HLA-DR by flow cytometry. Representative histograms (left panel) are depicted for each hormonal treatment (grey shaded areas); analysis of corresponding iDCs (grey line) and mDCs (black line) are shown in each histogram for control. In addition, statistical analysis of the mean fluorescence intensity (MFI) as a quantitative measure for surface expression levels is depicted as bar diagrams (right panel). n = 14.<p><b>Copyright information:</b></p><p>Taken from "The glycoprotein-hormones activin A and inhibin A interfere with dendritic cell maturation"</p><p>http://www.rbej.com/content/6/1/17</p><p>Reproductive biology and endocrinology : RB&E 2008;6():17-17.</p><p>Published online 6 May 2008</p><p>PMCID:PMC2412882.</p><p></p

The glycoprotein-hormones activin A and inhibin A interfere with dendritic cell maturation-3

Der different culture conditions with T lymphocytes at the indicated ratios. T-cell proliferation induced by iDCs, mDCs or DCs matured in the presence of Dex, TGF-β1, ActA or InA was measured on the basis of the measured optical density as described in the methods section. Mean +/- SEM; n = 8. At a DC:T ratio of 1:10, the reduction of the T-cell stimulatory capacity of the DCs was significantly reduced by all four hormones. Each bar represents n = 8 independent experiments.<p><b>Copyright information:</b></p><p>Taken from "The glycoprotein-hormones activin A and inhibin A interfere with dendritic cell maturation"</p><p>http://www.rbej.com/content/6/1/17</p><p>Reproductive biology and endocrinology : RB&E 2008;6():17-17.</p><p>Published online 6 May 2008</p><p>PMCID:PMC2412882.</p><p></p