Chorionic gonadotropin induces dendritic cells to express a tolerogenic phenotype.
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.
Wan
Hui
H
Department of Immunology, Erasmus MC, Dr. Molewaterplein 50, NL-3015 GE Rotterdam, The Netherlands. h.wan@erasmusmc.nl.
Versnel
Marjan A
MA
Leijten
Lonneke M E
LM
van Helden-Meeuwsen
Cornelia G
CG
Fekkes
Durk
D
Leenen
Pieter J M
PJ
Khan
Nisar A
NA
Benner
Robbert
R
Kiekens
Rebecca C M
RC
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D016207:Cytokines / Q000032:analysis; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D005269:Femur; D005434:Flow Cytometry; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D006063:Chorionic Gonadotropin; D016207:Cytokines