The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
The TLR-mediated response of plasmacytoid dendritic cells is positively regulated by estradiol in vivo through cell-intrinsic estrogen receptor α signaling
Open accessAbstract
Plasmacytoid dendritic cells (pDCs) produce large amounts of type I interferons (IFN-α/β) 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-α 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 17β-estradiol markedly enhances TLR-7– and TLR-9–dependent production of IFN-α 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) α. Genetic ablation of ERα gene in the DC lineage abrogated the enhancing effect of 17β-estradiol on their TLR-mediated production of IFN-α, 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.
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Cites
Plasmacytoid dendritic cells: sensing nucleic acids in viral infection and autoimmune diseases
Gilliet, M., Cao, W., & Liu, Y.-J. (2008) · Nature Reviews Immunology · doi:10.1038/nri2358 · Cited by 1,190
Calippe, B., Douin-Echinard, V., Delpy, L., Laffargue, M., Lélu, K., Krust, A., Pipy, B., Bayard, F., Arnal, J.-F., Guéry, J.-C., et al. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0902383 · Cited by 245
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Sex differences in immune responses
Klein, S. L., & Flanagan, K. L. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2016.90 · Cited by 6,370
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Sex differences in vaccine-induced humoral immunity
Fischinger, S., Boudreau, C. M., Butler, A. L., Streeck, H., & Alter, G. (2019) · Seminars in Immunopathology · doi:10.1007/s00281-018-0726-5 · Cited by 410
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Estrogen effects in allergy and asthma
Bonds, R. S., & Midoro-Horiuti, T. (2013) · Current Opinion in Allergy & Clinical Immunology · doi:10.1097/aci.0b013e32835a6dd6 · Cited by 208
Bruno, K. A., Mathews, J. E., Yang, A. L., Frisancho, J. A., Scott, A. J., Greyner, H. D., Molina, F. A., Greenaway, M. S., Cooper, G. M., Bucek, A., et al. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00598 · Cited by 73
Roberts, B. J., Dragon, J. A., Moussawi, M., & Huber, S. A. (2012) · Biology of Sex Differences · doi:10.1186/2042-6410-3-25 · Cited by 54
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Effect of age on chronic inflammation and responsiveness to bacterial and viral challenges
Elisia, I., Lam, V., Hofs, E., Li, M. Y., Hay, M., Cho, B., Brooks-Wilson, A., Rosin, M., Bu, L., Jia, W., et al. (2017) · PLOS ONE · doi:10.1371/journal.pone.0188881 · Cited by 34
Metadata
- Authors
- Seillet, C., Laffont, S., Trémollières, F., Rouquié, N., Ribot, C., Arnal, J.-F., Douin-Echinard, V., Gourdy, P., & Guéry, J.-C.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2012-01-12
- Volume
- 119
- Issue
- 2
- Pages
- 454-464
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2076092191
- Cited by
- 332
- References
- 2
- FWCI
- 4.42
- Type
- journal article
- Language
- en
- Open access
- bronze
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