| First Author | Seillet C | Year | 2012 |
| Journal | Blood | Volume | 119 |
| Issue | 2 | Pages | 454-64 |
| PubMed ID | 22096248 | Mgi Jnum | J:181798 |
| Mgi Id | MGI:5314190 | Doi | 10.1182/blood-2011-08-371831 |
| Citation | Seillet C, et al. (2012) The TLR-mediated response of plasmacytoid dendritic cells is positively regulated by estradiol in vivo through cell-intrinsic estrogen receptor alpha signaling. Blood 119(2):454-64 |
| abstractText | Plasmacytoid dendritic cells (pDCs) produce large amounts of type I interferons (IFN-alpha/beta) in response to viral or endogenous nucleic acids through activation of their endosomal Toll-like receptors (TLR-7 and TLR-9). Enhanced TLR-7-mediated IFN-alpha production by pDCs in women, compared with men, has been reported, but whether sex hormones, such as estrogens, are involved in this sex-based difference is unknown. Here we show, in humanized mice, that the TLR-7-mediated response of human pDCs is increased in female host mice relative to male. In a clinical trial, we establish that treatment of postmenopausal women with 17beta-estradiol markedly enhances TLR-7- and TLR-9-dependent production of IFN-alpha by pDCs stimulated by synthetic ligands or by nucleic acid-containing immune complexes. In mice, we found exogenous and endogenous estrogens to promote the TLR-mediated cytokine secretion by pDCs through hematopoietic expression of estrogen receptor (ER) alpha. Genetic ablation of ERalpha gene in the DC lineage abrogated the enhancing effect of 17beta-estradiol on their TLR-mediated production of IFN-alpha, showing that estrogens directly target pDCs in vivo. Our results uncover a previously unappreciated role for estrogens in regulating the innate functions of pDCs, which may account for sex-based differences in autoimmune and infectious diseases. |
