The effects of estrogen on the immune system are still largely unknown. We have investigated the effect of 17-estradiol (E 2 ) on human monocyte-derived immature dendritic cells (iDCs). Short-term culture in E 2 had no effect on iDC survival or the expression of cell surface markers. However, E 2 treatment significantly increased the secretion of interleukin 6 (IL-6) in iDCs and also increased secretion of osteoprotegerin (OPG) by DCs. Furthermore, E 2 significantly increased secretion of the inflammatory chemokines IL-8 and monocyte chemoattractant protein 1 (MCP-1) by iDCs, but not the production of the constitutive chemokines thymus and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC). However, after E 2 pretreatment the lipopolysaccharide (LPS)-induced production of MCP-1, TARC, and MDC by DCs was clearly enhanced. Moreover, mature DCs pretreated with E 2 stimulated T cells better than control cells. Finally, we found that E 2 provides an essential signal for migration
IntroductionDendritic cells (DCs) are key antigen-presenting cells (APCs), which recognize, capture, and process antigens, express costimulatory molecules, and then migrate to secondary lymphoid organs, where they can help initiate immune responses. 1 In addition to stimulating naive T cells and initiating primary immune responses, DCs act as effector cells in innate immunity and also play a role in maintaining peripheral tolerance. 2 DCs are also involved in T-cell polarization, for example, into T helper 1 (Th1) and Th2 cells. 2 For example, interleukin 12 (IL-12) secreted by DCs induces the production of interferon-␥ (IFN-␥) by CD4 ϩ T cells, which promotes Th1 cell differentiation and proliferation. 3 Furthermore, IL-6 derived from DCs can drive Th2 differentiation and at the same time inhibit Th1 polarization. [4][5][6] DCs can both produce and respond to chemokines, 7 which play a crucial role in leukocyte trafficking. 8 These include inflammatory, for example, IL-8 and monocyte chemoattractant protein 1 (MCP-1), as well as constitutive, eg, thymus and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC). 7 DC-derived chemokines not only are involved in T-cell priming and Th1/Th2-mediated responses, 9 but also contribute to the pathology of certain autoimmune conditions. 10,11 In many autoimmune diseases women are more likely to be affected than men. For example, in systemic lupus erythematosus (SLE), Sjögren syndrome, autoimmune thyroid disease, and scleroderma, more than 80% of the patients affected are women. 12 Sex hormones, particularly estrogen, may contribute to the pathogenesis of some autoimmune diseases. 13 Fluctuations in estrogen levels may correlate with disease status; for example, during pregnancy circulating levels of estrogen increase notably. 14 In both multiple sclerosis and rheumatoid arthritis, disease activity decreases during the third trimester when estrogen levels are highest and flares again when the estrogen levels decrease postpartum. 13 In SLE, however, th...