Progesterone, pregnancy, and innate immunity

Abstract

Progesterone plays an important role in the feto-maternal immunological relationship. The products of the progesterone-regulated genes Gal-1 and Hox-A10 affect dendritic cell (DC) function and differentiation of decidual NK cells, respectively. Progesterone favors the induction of immature DCs with a tolerogenic phenotype and inhibits the activity of mature DCs. Deficiency interferes with NK cell differentiation, while NK cell migration to the endometrium is supported by progesterone-induced specific endometrial production of chemokines. Progesterone upregulates HLA-G gene expression, which serves as a ligand for NK inhibitory and activating receptors. Many of the immunological effects of progesterone are mediated by a progesterone-induced protein called progesterone-induced blocking factor (PIBF). Progesterone and PIBF act on T cell differentiation to induce a Th2 dominance during pregnancy. Progesterone also promotes the development of LIF- as well as M-CSF-producing T cells. PIBF blocks upregulation of perforin expression in decidual lymphocytes cultured with decidual adherent cells and inhibits NK cell cytotoxicity by blocking granule exocytosis.