The Multi-faceted Influences of Estrogen on Lymphocytes: Toward Novel Immuno-interventions Strategies for Autoimmunity Management (original) (raw)

Estrogens and autoimmune diseases

ANNALS-NEW …

Abstract: Sex hormones are implicated in the immune response, with estrogens as enhancers at least of the humoral immunity and androgens and progesterone (and glucocorticoids) as natural immune-suppressors . Several physiological, pathological, and therapeutic conditions ...

Gender and Risk of Autoimmune Diseases: Possible Role of Estrogenic Compounds

Environmental Health Perspectives, 1999

A striking common feature of many autoimmune diseases in humans and experimental animals, despite differences in pathology, is that females are highly susceptible to autoimmune conditions compared to males. In several animal models, estrogens promote, whereas androgens abrogate, B-cell-mediated autoimmune diseases. To understand mechanisms by which estrogens regulate autoimmunity, it is first necessary to decipher estrogen effects on the normal immune system. Estrogen treatment of nonautoimmune mice diminished lymphocyte numbers in both developmental and mature lymphoid organs. Estrogen dysregulated T-and B-cell balance by inducing selective T-cell hypoactivity and B-cell hyperactivity. Even though estrogen did not alter the relative percentages of splenic T-cell subsets, splenic lymphocytes had a reduced proliferative response to T-cell stimulants and were refractory to rescue from activation-induced apoptosis compared to cells from placebo-treated mice. In contrast, estrogen induced B-cell hyperactivity (promoted autoantibodies to double-stranded DNA and phospholipids, increased numbers of plasma cells, and increased autoantibody yield per B cell). Note that treatment of normal mice with estrogen can alter T-and B-cell regulation and overcome B-cell tolerance to result in autoimmunity in normal individuals. Could environmental estrogens promote some human autoimmune disorders? Is there a link between environmental estrogens and autoimmune disorders, especially since these disorders are reported possibly more frequently? These provocative questions warrant investigation. Our findings on immunomodulatory effects may serve as a benchmark to examine whether endocrine-disrupting chemicals will have similar immunologic effects.

Estrogen, estrogen-like molecules and autoimmune diseases

Autoimmunity Reviews, 2020

In western countries, the slope of autoimmune disease (AD) incidence is increasing and affects 5-8% of the population. Mainly prevalent in women, these pathologies are due to thymic tolerance processes breakdown. The female sex hormone, estrogen, is involved in this AD female susceptibility. However, predisposition factors have to act in concert with unknown triggering environmental factors (virus, microbiota, pollution) to initiate AD. Individuals are exposed to various environmental compounds that display endocrine disruption abilities. The cellular effects of some of these molecules may be mediated through the aryl hydrocarbon receptor (AhR). Here, we review the effects of these molecules on the homeostasis of the thymic cells, the immune tolerance intrinsic factors (transcription factors, epigenetic marks) and on the immune tolerance extrinsic factors (microbiota, virus sensibility). This review highlights the contribution of estrogen and endocrine disruptors on the dysregulation of mechanisms sustaining AD development. The family of autoimmune diseases (AD) encompasses > 80 different chronic diseases, such as systemic lupus erythematosus (SLE), primary Sjӧgren's syndrome (SjS), rheumatoid arthritis (RA) and myasthenia gravis (MG). These pathologies affect 5 to 8% of the population, and their incidence is rising in industrialized countries. AD are more prevalent in women than in men and remain the fourth leading cause of illness for women [1-4]. The main role of the immune system is to distinguish self from nonself-components. A highly controlled process of establishing tolerance to self-antigens is set up in immune tissues (thymus and bone marrow) in order to maintain tissue and organ integrity. To effect this, the immune system must be able to identify autoreactive T-cells and eliminate them; otherwise autoimmune reactions can occur. Brooks has summarized this process into three key stages: 1) A breaking in central and peripheral mechanisms of tolerance to self-components; 2) defective immunoregulatory tools (defects in regulatory T-cells (Treg) and T helper cells 17 (Th17)); and 3) exposure to environmental induction factors. In this case, the adaptive immune response (via T-cells and B-cells) overreacts and may target the selfmolecules [5]. Numerous data corroborate that AD may arise when diverse events are combined to stimulate inflammation and finally activate abnormal immune signal reactions to targeted tissues or organs. Clear intrinsic factors are involved in disease progression, among them genetic factors single-nucleotide polymorphism (i.e., MHC genotypes), sex hormones and X chromosome inactivity defects. The contributions of extrinsic components have emerged from epidemiologic studies and investigations in monozygotic twins who display disease with incomplete concordance [6]. Hence, exposure to viruses [7], diet-related factors (vitamin D or gut microbiota), UV radiation, melatonin, lifestyle (job),

Sex hormones and the immune response in humans

Human Reproduction Update, 2005

In addition to their effects on sexual differentiation and reproduction, sex hormones appear to influence the immune system. This results in a sexual dimorphism in the immune response in humans: for instance, females produce more vigorous cellular and more vigorous humoral immune reactions, are more resistant to certain infections, and suffer a higher incidence of autoimmune diseases. Disease expression is also affected by the reproductive status of the female. As sex steroids-estrogens, progesterone and testosterone-differ between gender and within different reproductive stages, a lot of research has focussed on the effects of sex hormones on immune responses. Although there is also a vast literature on the effects of sex hormones on immune responses in animals, in this review we will focus on the most intriguing effects and mechanisms by which sex hormones affect different components of the immune system in humans.

Estrogen augments the T cell-dependent but not the T-independent immune response

Cellular and molecular …, 2010

Estrogen plays a critical regulatory role in the development and maintenance of immunity. Its role in the regulation of antibody synthesis in vivo is still not completely clear. Here, we have compared the effect of estrogen on T cell-dependent (TD) and T cell-independent type 2 (TI-2) antibody responses. The results provide the first evidence that estrogen enhances the TD but not the TI-2 response. Ovariectomy significantly decreased, while estrogen re-administration increased the number of haptenspecific IgM-and IgG-producing cells in response to TD antigen. In vitro experiments also show that estrogen may have a direct impact on B and T cells by inducing rapid signaling events, such as Erk and AKT phosphorylation, cell-specific Ca 2? signal, and NFjB activation. These nontranscriptional effects are mediated by classical estrogen receptors and partly by an as yet unidentified plasma membrane estrogen receptor. Such receptor-mediated rapid signals may modulate the in vivo T cell-dependent immune response.

Dimorphic Modulation of Immunity: From Gender to Hormones

2018

The open circuit system of immunity is composed of different cellular and non-cellular components. However, the components are seemingly limited in view of their multifaceted actions. Hence, the particularity and functional diversity of immune system lie in the mode of regulation of all of its components. There are different factors which regulate the proper function and modus operandi of several components of immune system. Among them, one most important factor is regulation through hormones. There are different classes of hormones, but in context of immune system, hormones are immune-enhancing, immune-inhibitory, or immune-neutral. In-depth studies have shown that response of immune system varies with hormones of different kinds. It depends on the context (in vivo and in vitro), nature of hormone (steroid, proteinaceous, peptide, amino acid, and amino acid derivative), body condition (healthy vs. under pathological/clinical), and their behavior when in combination with other hormo...

Sex hormones and immune dimorphism

TheScientificWorldJournal, 2014

The functioning of the immune system of the body is regulated by many factors. The abnormal regulation of the immune system may result in some pathological conditions. Sex hormones of reproductive system are one of the major factors that regulate immune system due to the presence of hormone receptors on immune cells. The interaction of sex hormones and immune cells through the receptors on these cells effect the release of cytokines which determines the proliferation, differentiation, and maturation of different types of immunocytes and as a result the outcome of inflammatory or autoimmune diseases. The different regulations of sex hormones in both sexes result in immune dimorphism. In this review article the mechanism of regulation of immune system in different sexes and its impact are discussed.

Sexual dimorphism in immune function: The role of sex steroid hormones

SHS Web of Conferences, 2018

There is evidence of the relation of sex steroid hormones and sexual dimorphism in immune system response to infectious diseases. The aim of this review was to identify the role of sex hormones in immune function and sexual dimorphism of immune reactions. Gonadal hormones together with the immune system play an important role in process of immune responses to the disease [1]. Estrogens, progesterone and testosterone have different impacts on immune cells and different gonadal hormones are of high importance for responses of innate and adaptive immunity [1, 2]. Estrogens mainly enhance immune function while testosterone has a suppressive role. Higher progesterone during pregnancy leads to autoimmune disease remission and an elevated susceptibility toward certain infectious diseases [2, 3, 4]. The intensity and prevalence of viral infections are typically higher in males, whereas disease outcome could be worse for females [5]. Sexual dimorphism of immune function is based on different...