Estrogen and estrogen receptor signaling promotes allergic immune responses: Effects on immune cells, cytokines, and inflammatory factors involved in allergy

Zhang, Fan; Che, Huilian; Yang, Sijia; Chen, Chongxiao

doi:10.1016/j.aller.2019.03.001

Cited by 23 publications

(26 citation statements)

References 72 publications

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“…Estrogen receptors are found on numerous immune-regulatory cells, with estrogen-dependent responses favoring the shift toward allergy. In particular, estrogens promote allergic response by stimulating Th2 polarization, boosting class switching of B cells to IgE production, and prompting mast cell and basophil degranulation ( 51 ). ESR2 and its product, estrogen receptor β, have been suggested as potential targets for asthma treatment ( 52 ).…”

Section: Discussionmentioning

confidence: 99%

Shared Genetic Liability Between Major Depressive Disorder and Atopic Diseases

Cao

Baranova

et al. 2021

Front. Immunol.

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ObjectivesDeciphering the genetic relationships between major depressive disorder (MDD) and atopic diseases (asthma, hay fever, and eczema) may facilitate understanding of their biological mechanisms as well as the development of novel treatment regimens. Here we tested the genetic correlation between MDD and atopic diseases by linkage disequilibrium score regression.MethodsA polygenic overlap analysis was performed to estimate shared genetic variations between the two diseases. Causal relationships between MDD and atopic diseases were investigated using two-sample bidirectional Mendelian randomization analysis. Genomic loci shared between MDD and atopic diseases were identified using cross-trait meta-analysis. Putative functional genes were evaluated by fine-mapping of transcriptome-wide associations.ResultsThe polygenic analysis revealed approximately 15.8 thousand variants causally influencing MDD and 0.9 thousand variants influencing atopic diseases. Among these variants, approximately 0.8 thousand were shared between the two diseases. Mendelian randomization analysis indicates that genetic liability to MDD has a causal effect on atopic diseases (b = 0.22, p = 1.76 × 10-6), while genetic liability to atopic diseases confers a weak causal effect on MDD (b = 0.05, p = 7.57 × 10-3). Cross-trait meta-analyses of MDD and atopic diseases identified 18 shared genomic loci. Both fine-mapping of transcriptome-wide associations and analysis of existing literature suggest the estrogen receptor β-encoding gene ESR2 as one of the potential risk factors for both MDD and atopic diseases.ConclusionOur findings reveal shared genetic liability and causal links between MDD and atopic diseases, which shed light on the phenotypic relationship between MDD and atopic diseases.

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Section: Discussionmentioning

confidence: 99%

Shared Genetic Liability Between Major Depressive Disorder and Atopic Diseases

Cao

Baranova

et al. 2021

Front. Immunol.

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“…On the other hand, Klis & Wronka, 2017, observed a higher risk of allergic rhinitis in women with greater exposure to estrogen. It is well known that estrogen plays an important involvement in immune response of allergic diseases through specific receptors acting in some cells as: Th2, B cells, basophilic cells, and mast cells (Fan, Che, Yang, & Chen, 2019), as cited before.…”

Section: Estrogen and Its Impact In Nasal Mucosamentioning

confidence: 94%

Estrogen receptors and their roles in the immune and respiratory systems

Millas

Barros²

2021

The Anatomical Record

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Estrogen is an important hormone for health in both genders. It is indispensable to glucose homeostasis, immune robustness, bone health, cardiovascular health, and neural functions. The main way that estrogen acts in the cells is through estrogen receptors (ERs). The presence of specific estrogen receptors is required for estrogen to have its characteristic ubiquitous action in almost all tissues. Estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) are the major isoforms of estrogen that are highly specific in humans and enable selective hormonal actions in different tissues. This article reviews some of the observed estrogen actions and effects in different tissues and cells through these specific receptors. This ubiquitous, almost ordinary hormone may reveal itself as a significant factor that helped us to better understand the complexity of the human immune system response against respiratory infections, including the COVID-19, and especially in the current state of this painful pandemic.

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“…The skewing of the allergic response to the COVID mRNA vaccine toward the female sex may be secondary to estrogen effects in promoting a T H 2 response, or conversely, testosterone and progesterone's known role in diminishing T H 2 responses. 54,55 In addition, sex hormones may influence mast cell degranulation; although estrogen is thought to be stimulatory, studies demonstrate that progesterone suppresses histamine release from mast cells. 55,56 Estrogen has also been demonstrated to increase endothelial nitric oxide synthase activity, enhancing the severity of anaphylaxis in murine studies.…”

Section: Host Factors Leading To Mast Cell Hyperresponsivenessmentioning

confidence: 99%

“…54,55 In addition, sex hormones may influence mast cell degranulation; although estrogen is thought to be stimulatory, studies demonstrate that progesterone suppresses histamine release from mast cells. 55,56 Estrogen has also been demonstrated to increase endothelial nitric oxide synthase activity, enhancing the severity of anaphylaxis in murine studies. 57 An investigation into the discrepant role of sex hormones in this setting is critical for understanding the pathogenesis and potentially developing tools to screen for or prevent reactions.…”

Section: Host Factors Leading To Mast Cell Hyperresponsivenessmentioning

confidence: 99%

Potential mechanisms of anaphylaxis to COVID-19 mRNA vaccines

Risma

Edwards

Hummell

et al. 2021

Journal of Allergy and Clinical Immunology

128

133

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Anaphylaxis to vaccines is historically a rare event. The Coronavirus Disease 2019 (COVID-19) pandemic drove the need for rapid vaccine production applying a novel antigen delivery system: mRNA vaccines packaged in lipid nanoparticles (LNP). Unexpectedly, public vaccine administration led to a small number of severe allergic reactions with resultant substantial public concern, especially within atopic individuals. We reviewed the constituents of the mRNA LNP vaccine and considered several contributors to these reactions: 1) contact system activation by nucleic acid, 2) complement recognition of the vaccine activating allergic effector cells, 3) pre-existing antibody recognition of polyethylene glycol (PEG), a LNP surface hydrophilic polymer, and 4) direct mast cell activation, coupled with potential genetic or environmental predispositions to hypersensitivity. Unfortunately, measurement of anti-PEG antibodies in vitro is not clinically available, and the predictive value of skin testing to PEG components as a COVID-19 mRNA vaccine-specific anaphylaxis marker is unknown. Even less is known regarding the applicability of vaccine use for testing (in vitro/vivo) to ascertain pathogenesis or predict reactivity risk. Expedient and thorough research-based evaluation of patients who have suffered anaphylactic vaccine reactions and prospective clinical trials in putative at-risk individuals are needed to address these concerns during a public health crisis.

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Estrogen and estrogen receptor signaling promotes allergic immune responses: Effects on immune cells, cytokines, and inflammatory factors involved in allergy

Cited by 23 publications

References 72 publications

Shared Genetic Liability Between Major Depressive Disorder and Atopic Diseases

Shared Genetic Liability Between Major Depressive Disorder and Atopic Diseases

Estrogen receptors and their roles in the immune and respiratory systems

Potential mechanisms of anaphylaxis to COVID-19 mRNA vaccines

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