Mechanisms of sex hormones in autoimmunity: focus on EAE

Lasrado, Ninaad; Jia, Ting; Massilamany, Chandirasegaran; Franco, Rodrigo; Illés, Zsolt; Reddy, Jay

doi:10.1186/s13293-020-00325-4

Cited by 27 publications

(31 citation statements)

References 192 publications

(205 reference statements)

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“… 89 , 90 Autoimmune rheumatic and endocrine disorders such as rheumatic arthritis, systemic lupus erythematosus, antiphospholipid syndrome, Sjøgren-syndrome, and thyroid disorders are more prevalent in women than in men and are associated with an increased CVD risk. 91–94 Patients with these disorders also have a higher clustering of traditional risk factors. 95 These risk variables should be taken into consideration when assessing individual risk around menopause.…”

Section: Menopause Cardiovascular Disease Risk Factors and Ischaemimentioning

confidence: 99%

Cardiovascular health after menopause transition, pregnancy disorders, and other gynaecologic conditions: a consensus document from European cardiologists, gynaecologists, and endocrinologists

Maas

Rosano

Cífková

et al. 2021

European Heart Journal

196

128

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Women undergo important changes in sex hormones throughout their lifetime that can impact cardiovascular disease risk. Whereas the traditional cardiovascular risk factors dominate in older age, there are several female-specific risk factors and inflammatory risk variables that influence a woman’s risk at younger and middle age. Hypertensive pregnancy disorders and gestational diabetes are associated with a higher risk in younger women. Menopause transition has an additional adverse effect to ageing that may demand specific attention to ensure optimal cardiovascular risk profile and quality of life. In this position paper, we provide an update of gynaecological and obstetric conditions that interact with cardiovascular risk in women. Practice points for clinical use are given according to the latest standards from various related disciplines (Figure 1).

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Section: Menopause Cardiovascular Disease Risk Factors and Ischaemimentioning

confidence: 99%

Cardiovascular health after menopause transition, pregnancy disorders, and other gynaecologic conditions: a consensus document from European cardiologists, gynaecologists, and endocrinologists

Maas

Rosano

Cífková

et al. 2021

European Heart Journal

196

128

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“…Sex-dependent inflammatory phenotypes are observed in response to innate and adaptive immune reactions as well as in acute and chronic inflammatory diseases and their animal models ( Klein and Flanagan, 2016 ; Chamekh and Casimir, 2019 ; Gal-Oz et al, 2019 ). Males are generally more susceptible to pathogen infections ( Klein, 2012 ; Vazquez-Martinez et al, 2018 ), while females are more often diagnosed with autoimmune diseases ( Quintero et al, 2012 ; Ngo et al, 2014 ; Billi et al, 2019 ; Lasrado et al, 2020 ). For example, in experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis, female and male mice have differing disease courses ( Constantinescu et al, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

Estrogen Receptor β as a Candidate Regulator of Sex Differences in the Maternal Immune Activation Model of ASD

Arnold

Saijo

2021

Front. Mol. Neurosci.

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Interestingly, more males are diagnosed with autism spectrum disorder (ASD) than females, yet the mechanism behind this difference is unclear. Genes on the sex chromosomes and differential regulation by sex steroid hormones and their receptors are both candidate mechanisms to explain this sex-dependent phenotype. Nuclear receptors (NRs) are a large family of transcription factors, including sex hormone receptors, that mediate ligand-dependent transcription and may play key roles in sex-specific regulation of immunity and brain development. Infection during pregnancy is known to increase the probability of developing ASD in humans, and a mouse model of maternal immune activation (MIA), which is induced by injecting innate immune stimulants into pregnant wild-type mice, is commonly used to study ASD. Since this model successfully recaptures the behavioral phenotypes and male bias observed in ASD, we will discuss the potential role of sex steroid hormones and their receptors, especially focusing on estrogen receptor (ER)β, in MIA and how this signaling may modulate transcription and subsequent inflammation in myeloid-lineage cells to contribute to the etiology of this neurodevelopmental disorder.

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“…Overall, sex hormones can directly modulate effector lymphocyte responses, resulting in altered immune CNS infiltration, tissue damage, and altered balance of pro‐inflammatory versus regulatory cell types (Lasrado et al., 2020; Wiedrick et al., 2021).…”

Section: Gender‐related Modulation Of Neuroinflammationmentioning

confidence: 99%

“…Gender‐related differences in the occurrence of autoimmune diseases is well documented, with females showing a greater propensity to develop Hashimoto's thyroiditis (female to male ratio of 19:1), Sjögren's syndrome (16:1), systemic lupus erythematosus (7:1), Grave's disease (7:1), rheumatoid arthritis (RA) (3:1), and MS (2:1) (Beeson, 1994; Brandt, Priori, Valesini, & Fairweather, 2015; Gleicher & Barad, 2007; Lasrado et al., 2020; Magyari, 2016)…”

Section: Gender‐related Modulation Of Neuroinflammationmentioning

confidence: 99%

Animal Models of Multiple Sclerosis

Smith

2021

Current Protocols

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Animal models with high translational validity are essential tools in understanding disease pathogenesis and in the development of therapeutic strategies. Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system characterized by progressive neurological deficits and socioeconomic burden. Experimental autoimmune encephalomyelitis (EAE) is the most extensively utilized animal model of MS, with well‐characterized rodent and non‐human primate variants. The EAE model is typically induced by either active immunization with myelin‐derived proteins or peptides in adjuvant or by passive transfer of activated myelin‐specific CD4+ T lymphocytes. To date, the EAE model has been an essential tool in the development of at least seven U.S. Food and Drug Administration (FDA)−approved immunomodulatory drugs for the treatment of MS, including glatiramer acetate, fingolimod, and natalizumab. However, the translational validity of the EAE model is frequently compromised due to poor study design, inconsistent clinical scoring endpoints, and inappropriate statistical calculations. No single animal model accurately reflects the complexity of human MS pathogenesis. Beyond EAE, multiple additional animal models are described, including Theiler's murine encephalomyelitis virus and cuprizone‐induced demyelination, which facilitate the study of pathogen‐induced CNS autoimmunity and remyelination, respectively. This overview summarizes several of the most frequently used animal models of MS and highlights key factors that significantly influence the experimental outcome and affect translational validity. © 2021 Wiley Periodicals LLC.

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Mechanisms of sex hormones in autoimmunity: focus on EAE

Cited by 27 publications

References 192 publications

Cardiovascular health after menopause transition, pregnancy disorders, and other gynaecologic conditions: a consensus document from European cardiologists, gynaecologists, and endocrinologists

Cardiovascular health after menopause transition, pregnancy disorders, and other gynaecologic conditions: a consensus document from European cardiologists, gynaecologists, and endocrinologists

Estrogen Receptor β as a Candidate Regulator of Sex Differences in the Maternal Immune Activation Model of ASD

Animal Models of Multiple Sclerosis

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