Development of Myeloid Dendritic Cells under the Influence of Sexual Hormones Visualized using Scanning and Transmission Electron Microscopy

Dendritic cells (DCs) are antigen-presenting cells, which are mediated by MHC-class II molecules reacting with T-helper cells, eliciting a broad spectrum of immune reactions at cellular and humoral levels depending on their subtypes. DCs are also able to cross-present peptides from intracellular proteins as well as from intracellular pathogens via MHC-class I molecules by inducing MHC-class I–restricted cytotoxic T cells, which are also able to destroy cells undergoing malignant transformation. DCs originate from CD34+ hematopoietic stem cells but can also develop from monocytes. The local or systemic milieu of cytokines and steroid hormones significantly influences the generation of particular DC subtypes such as the classical myeloid DCs such as cDC1 and cDC2 as well as the plasmacytoid DCs. These subtypes are able to induce specific Th1- and Th17-dependent, Th2-dependent, or regulatory immune responses, respectively. Immature DCs take up extracellular pathogens that are presented by MHC molecules that are upregulated during maturation. Immature and mature DCs can be characterized by morphological and biochemical features that are outlined in this article. In addition, DCs are under control of sexual hormones. Estrogen receptor ligands are potent modulators of hemopoiesis and immune function in health and disease, influencing key cytokines promoting the maturation of DCs. DC differentiation is mainly regulated by binding of estradiol to ERα. Estrogen promotes the differentiation of immature DC subsets derived from bone marrow precursors or from myeloid progenitors. In contrast to estrogen, progesterone inhibits DC maturation, causing a decreased immunity in pregnancy or in postmenopausal women, where elevated levels of progesterone result in the production of Th2 cytokines. The influence of estrogen and progesterone on DC maturation has been demonstrated in own in vitro experiments using fluorescence microscopy and cell sorting and, above all, by visualization using SEM and TEM. At the end of this article, pits and falls concerning the treatment of malignancies with living DC vaccines are discussed.