Estrogens and Dendritic Cells


A study published in the Journal of Immunology demonstrates that estrogens may boost innate immunity by enhancing interferon (IFN)-γ production by CD11c(+) dendritic cells.

In humans, the sex differences or the sexual dimorphism in immune defense is a well-known phenomenon. Females have more vigorous cellular and humoral immune responses, and they are more resistant to infections – the prevalence and intensity of viral, bacterial, and parasitic infections are typically reduced in females compared with males.

Importantly, females are more prone to autoimmune diseases. Thus, nearly 80% of autoimmunity patients in the U.S. are women.

Sex hormones such as estrogens directly affect immunity and estrogen receptors are expressed on circulating lymphocytes, dendritic cells (DCs), NK cells, and macrophages. Previous research indicates that estrogens are able to facilitate the production of IFN-γ by NK cells.

In addition, recent research indicates that estradiol acting on DCs may harbor more open chromatin at genes encoding innate immune signaling intermediates and type I IFN than DCs in male mice. This might explain the more robust production of type I IFN observed in females.

In the Journal of Immunology study, Mark Siracusa and colleagues from the Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA demonstrate that E2 promoted the differentiation of bone marrow precursor cells into functional CD11c+CD11b+MHC class II+ DCs.

Importantly, the authors found that CD11c+ splenocytes isolated from animals with supplemental E2 produced more IFN-γ in response to IL-12 and IL-18. Of note, preceding work shows that CD11c(+)NK1.1(+) cells are a significant source of IFN-γ production, and this IFN-γ is vital for the protection against intracellular infections.

Thus, the study of Siracusa et al. may indicate that the up-regulated production of IFN-γ by CD11c(+) cells in response to 17β-estradiol stimulation may boost innate and adaptive immune responses.

This observation may provide an important mechanism regulating differences in the prevalence of autoimmune diseases and susceptibility to infection between sexes.

Source: J Immunol 2008, 180:1423
Read more: Journal of Immunology

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