To reconcile immunity and reproduction, females must allow spermatozoa to survive and control the presence of commensal microbiota and sexually transmitted pathogens during ovulation. Female steroid sex hormones exert a powerful effect on the immune system, as do the hormonal changes associated with the ovarian cycle. Dendritic cells (DCs) are immunological sentinels that link innate immunity to adaptive immunity. Upon exposure to microbial invaders in tissue, they undergo a maturational process that culminates in the lymph nodes and activates T-cell-specific immune responses. Estradiol, which is highly expressed during ovulation, has an effect on the maturation of DCs, although the molecular mechanism remains elusive. We detected that estradiol regulates expression of Ikbkg in DCs and modulates nuclear factor-κb translocation to the nucleus, thus explaining the reduced DC function observed during ovulation. This change may be an adaptive mechanism to reconcile control of infection and reproductive functions.
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We are grateful to the units of confocal microscopy, flow cytometry and statistical analysis, as well as to the animal facility of the Instituto de Investigación Sanitaria Gregorio Marañón, for their help and support. R. Madrid, V. Briz, M. Martínez-Bonet, and R. Gonzalez-Dosal provided corrections and comments. F. Sanchez-Cobos provided technical support. This work was supported by research grants from Instituto de Salud Carlos III (ISCIII) (PI10/00897) and Fundacion Mutua Madrileña (awarded to MR). MR holds a Miguel Servet contract from the ISCIII (CP08/00228). MAMF hold grants from the ISCIII (INTRASALUD PI09/02029). LALF holds a Miguel Servet contract from ISCIII (CP06/00267).
The authors declare no conflicts of interest.
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Lasarte, S., Elsner, D., Sanchez-Elsner, T. et al. Estradiol downregulates NF-κb translocation by Ikbkg transcriptional repression in dendritic cells. Genes Immun 14, 462–469 (2013). https://doi.org/10.1038/gene.2013.35
- dendritic cells.