Glucocorticoid Receptor Mediates the Effect of Progesterone on Uterine Natural Killer Cells

Guo, Wei; Li, Pengfei; Zhao, Guangfeng; Fan, Hong; Hu, Yali; Hou, Yayi

doi:10.1111/j.1600-0897.2012.01114.x

Cited by 49 publications

(38 citation statements)

References 44 publications

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“…In fact, the negative correlation with this activated non-CD4 + lymphocyte was the strongest in females. The selective nature of progesterone is in concordance with reported evidence of progesterone suppression of uterine natural killer (NK) cells in human and spleen cells in mice expressing CD69 (52). In females, this population of cells appeared to be responsive to the effect of progesterone and resulted in reduced percentages in subjects increased for progesterone.…”

Section: Discussionsupporting

confidence: 86%

Sexual Dimorphic Responses in Lymphocytes of Healthy Individuals after Carica papaya Consumption

et al. 2017

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Sexual dimorphism in immune response is widely recognized, but few human studies have observed this distinction. Food with endo-immunomodulatory potential may reveal novel sex-biased in vivo interactions. Immunomodulatory effects of Carica papaya were compared between healthy male and female individuals. Volunteers were given fixed meals supplemented with papaya for 2 days. Changes in blood immune profiles and hormone levels were determined. In females, total natural killer (NK) cell percentages decreased (12.7 ± 4.4 vs 14.6 ± 5.8%, p = 0.018, n = 18) while B cells increased (15.2 ± 5.5 vs 14.5 ± 5.0, p = 0.037, n = 18) after papaya consumption. Increased 17β-estradiol (511.1 ± 579.7 vs 282.7 ± 165.0 pmol/l, p = 0.036, n = 9) observed in females may be crucial to this change. Differentiation markers (CD45RA, CD69, CD25) analyzed on lymphocytes showed naïve (CD45RA+) non-CD4+ lymphocytes were reduced in females (40.7 ± 8.1 vs 46.8 ± 5.4%, p = 0.012, n = 8) but not males. A general suppressive effect of papaya on CD69+ cells, and higher percentage of CD69+ populations in females and non-CD4 lymphocytes, may be relevant. CD107a+ NK cells were significantly increased in males (16.8 ± 7.0 vs 14.7 ± 4.8, p = 0.038, n = 9) but not females. Effect in females may be disrupted by the action of progesterone, which was significantly correlated with this population (R = 0.771, p = 0.025, n = 8) after papaya consumption. In males, total T helper cells were increased (33.4 ± 6.4 vs 32.4 ± 6.1%, p = 0.040, n = 15). Strong significant negative correlation between testosterone and CD25+CD4+ lymphocytes, may play a role in the lower total CD4+ T cells reported in males. Thus, dissimilar immune profiles were elicited in the sexes after papaya consumption and may have sex hormone influence.

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Section: Discussionsupporting

confidence: 86%

Sexual Dimorphic Responses in Lymphocytes of Healthy Individuals after Carica papaya Consumption

et al. 2017

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“…Additionally, RU-486 inhibited suppressive effect of P4 on IFN-γ mRNA expression in uNK cells stimulated with CpG and IL-12. The same effect was observed in murine splenic NK cells isolated in diestrus [20]. …”

Section: Introductionsupporting

confidence: 70%

Lack of in vitro effect of aglepristone on IFN-γ and IL-4 production by resting and mitogen-activated T cells of luteal bitches

et al. 2013

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BackgroundAglepristone (RU534) is an antiprogestin used for pregnancy termination, parturition induction and conservative pyometra treatment in bitches. Its molecular structure is similar to mifepristone, an antiprogestin used in human medicine. Mifepristone has been shown to suppress proliferation and cytokine production by T cells, whereas the effect of aglepristone on T cell function remains elusive. The purpose of this project was to investigate the in vitro influence of RU534 on IFN-γ and IL-4 synthesis by peripheral blood T cells isolated from healthy bitches (N = 16) in luteal phase. The peripheral blood mononuclear cells (PBMCs) were incubated with three different dosages of aglepristone, or dimethyl sulfoxide (DMSO), with or without mitogen. The production of cytokines by resting or mitogen-activated T cells was determined by intercellular staining and flow cytometry analysis or ELISA assay, respectively.ResultsOur results showed no statistically significant differences in the percentage of IFN-γ and IL-4-synthesizing CD4+ or CD8+ resting T cells between untreated and aglepristone-treated cells at 24 and 48 hours post treatment. Moreover, mitogen-activated PBMCs treated with RU534 displayed similar concentration of IFN-γ and IL-4 in culture supernatants to those observed in mitogen-activated DMSO-treated PBMCs. Presented results indicate that administration of aglepristone for 48 hours has no influence on IFN-γ and IL-4 synthesis by resting and mitogen-activated T cells isolated from diestral bitches.ConclusionsWe conclude that antiprogestins may differentially affect T cell function depending on the animal species in which they are applied.

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“…Interestingly, mature human and rodent uNK cells do not express steroid receptors (55, 62–64). Thus, it is suggested that, at least for P4, effects are mediated through the glucocorticoid receptor (GR), proven to be expressed on murine uNK cells (65). In addition to the lack of steroid receptors, uNKs also miss the classical LH/CG receptor.…”

Section: Hormonal Influence On Immune Cells During Pregnancymentioning

confidence: 99%

Endocrine Factors Modulating Immune Responses in Pregnancy

2014

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How the semi-allogeneic fetus is tolerated by the maternal immune system remains a fascinating phenomenon. Despite extensive research activity in this field, the mechanisms underlying fetal tolerance are still not well understood. However, there are growing evidences that immune–immune interactions as well as immune–endocrine interactions build up a complex network of immune regulation that ensures fetal survival within the maternal uterus. In the present review, we aim to summarize emerging research data from our and other laboratories on immune modulating properties of pregnancy hormones with a special focus on progesterone, estradiol, and human chorionic gonadotropin. These pregnancy hormones are critically involved in the successful establishment, maintenance, and termination of pregnancy. They suppress detrimental maternal alloresponses while promoting tolerance pathways. This includes the reduction of the antigen-presenting capacity of dendritic cells (DCs), monocytes, and macrophages as well as the blockage of natural killer cells, T and B cells. Pregnancy hormones also support the proliferation of pregnancy supporting uterine killer cells, retain tolerogenic DCs, and efficiently induce regulatory T (Treg) cells. Furthermore, they are involved in the recruitment of mast cells and Treg cells into the fetal–maternal interface contributing to a local accumulation of pregnancy-protective cells. These findings highlight the importance of endocrine factors for the tolerance induction during pregnancy and encourage further research in the field.

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Glucocorticoid Receptor Mediates the Effect of Progesterone on Uterine Natural Killer Cells

Abstract: In the present study, we first prove that progesterone can regulate NK cells via GR. It is valuable for further understanding the role of uNK in progesterone regulated gestation process.

Cited by 49 publications

References 44 publications

Sexual Dimorphic Responses in Lymphocytes of Healthy Individuals after Carica papaya Consumption

Sexual Dimorphic Responses in Lymphocytes of Healthy Individuals after Carica papaya Consumption

Lack of in vitro effect of aglepristone on IFN-γ and IL-4 production by resting and mitogen-activated T cells of luteal bitches

Endocrine Factors Modulating Immune Responses in Pregnancy

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