Chorionic gonadotropin induces dendritic cells to express a tolerogenic phenotype

Abstract

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.

Human Chorionic Gonadotropin as a Central Regulator of Pregnancy Immune Tolerance

“…In addition, it has been shown that P induces an immature phenotype in bone marrow-derived DCs (51) and estrogen reduces the production of inflammatory cytokines by mature DCs (52), suggesting that pregnancy hormones may also influence DC phenotype and activity. In terms of an hCG-mediated effect on DCs, in vitro data are quite controversial (48,53,54) and in vivo data are not available yet.…”

“…In this regard, the secretion of IL-10 seems to be an essential mechanism for DC function at the fetal-maternal interface as IL-10 directly inhibits effector T cells (57) and promotes Treg generation (36). Segerer and colleagues (54), as well as Wan and colleagues (53), nicely showed in vitro that hCG inhibits upregulation of MHC class II molecules on DCs, reduces their T cell stimulatory capacity, and induces IL-10 production. By contrast, Yoshimura and colleagues (48) revealed that hCG induces the maturation of myeloid and lymphoid DCs in conjunction with increases in the expression of adhesion/costimulatory molecules, their stimulatory activities in MLR, and cytokine secretion.…”

The Special Implication of Sex Hormones on Dendritic Cells During Pregnancy

“…Investigations on DC demonstrated hCG receptors to be constitutively expressed by these cells which allows a direct activation of DC via hCG (Yoshimura, Inaba et al, 2003). Experiments on mouse DC revealed that hCG acts in an immunregulatory way by increasing the production of immunosuppressive factors like Interleukin-10 (IL-10) by DC and by reducing antigen-specific T-cell proliferation (Wan, Versnel et al, 2008). In humans, hCG was also able to significantly decrease T-cell stimulatory capacity of DC (Huck, Steck et al, 2005).…”

Two Concepts on the Immunological Aspect of Blastocyst Implantation

“…This enzyme breaks tryptophan down to N-formylkynurenine, and prevents the activation of lymphocytes. Wan et al [35] hypothesized that hCG is involved in the maternal-fetal immune tolerance by the regulation of dendritic cell function. They showed that hCG decreased cytokine production by dendritic cells and inhibited the ability of dendritic cells to stimulate T cell proliferation.…”