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Originally published online as doi:10.1189/jlb.0407258 on January 2, 2008

Published online before print January 2, 2008
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(Journal of Leukocyte Biology. 2008;83:894-901.)
© 2008 by Society for Leukocyte Biology

Chorionic gonadotropin induces dendritic cells to express a tolerogenic phenotype

Hui Wan*,1, Marjan A. Versnel*, Lonneke M. E. Leijten*, Cornelia G. van Helden-Meeuwsen*, Durk Fekkes{dagger}, Pieter J. M. Leenen*, Nisar A. Khan*, Robbert Benner* and Rebecca C. M. Kiekens*

* Departments of Immunology and
{dagger} Neuroscience and Psychiatry, Erasmus MC, Rotterdam, The Netherlands

1 Correspondence: Department of Immunology, Erasmus MC, Dr. Molewaterplein 50, NL-3015 GE Rotterdam, The Netherlands. E-mail: h.wan{at}erasmusmc.nl

The pregnancy hormone human chorionic gonadotropin (hCG) has been suggested to play an immunoregulatory role in addition to its endocrine function, thus contributing to the prevention of fetal rejection. We hypothesized that hCG is involved in the maternal-fetal immune tolerance by the regulation of dendritic cell (DC) function. Therefore, we studied the effect of hCG on DC maturation. Upon hCG treatment in combination with LPS, mouse bone marrow-derived DC (BMDC) increased the ratio of IL-10:IL-12p70, down-regulated TNF-{alpha}, and decreased antigen-specific T cell proliferation. Addition of hCG together with LPS and IFN-{gamma} blocked MHC class II up-regulation, increased IL-10 production, and decreased the antigen-specific T cell proliferation by DC. Splenic DC showed similar results. Upon hCG treatment, IDO mRNA expression and its metabolite kynurenine were increased by LPS- and IFN-{gamma}-stimulated DC, suggesting its involvement in the decreased T cell proliferation. To study the effect of hCG on DC differentiation from precursors, BMDC were generated in the continuous presence of hCG. Under this condition, hCG decreased cytokine production and the induction of T cell proliferation. These data are suggestive for a contribution of hCG to the maternal-fetal tolerance during pregnancy by modifying DC toward a tolerogenic phenotype.

Key Words: hCG • DC • IDO • tolerance




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