Expression of X-linked Toll-like receptor 4 signaling genes in female vs. male neonates

O'Driscoll, David N; Santi, Chiara De; McKiernan, Paul J; McEneaney, Victoria; Molloy, Eleanor J.; Greene, Catherine M.

doi:10.1038/pr.2017.2

Cited by 23 publications

(19 citation statements)

References 33 publications

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“…4D). Female neonates have higher levels of IRAK1 mRNA and protein in cord blood and mononucleated cells compared to males 47 , potentially contributing to reduced infection rates and female-specific immune advantages in infants. However, these scRNAseq analyses are limited by the fact that the sample was taken from one individual and does not contain in vivo stimulated B cells, which may have distinct XCI escape profiles.…”

Section: Discussionmentioning

confidence: 99%

The dynamic epigenetic regulation of the inactive X chromosome in healthy human B cells is dysregulated in lupus patients

Pyfrom

Paneru

Knoxx

et al. 2020

Preprint

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Systemic lupus erythematous (SLE) is a female-predominant disease characterized by autoimmune B cells and pathogenic autoantibody production. Individuals with two or more X chromosomes are at increased risk for SLE, suggesting that X-linked genes contribute to the observed sex-bias of this disease. To normalize X-linked gene expression between sexes, one X in female cells is randomly selected for transcriptional silencing through X-Chromosome Inactivation (XCI), resulting in allele-specific enrichment of epigenetic modifications, including histone methylation and the long noncoding RNA XIST/Xist on the inactive X (Xi). As we have previously shown that epigenetic regulation of the Xi in female lymphocytes from mice is unexpectedly dynamic, we used RNA FISH and immunofluorescence to profile epigenetic features of the Xi at the single cell level in human B cell subsets from pediatric and adult SLE patients and healthy controls. Our data reveal that abnormal XCI maintenance in B cells is a feature of SLE. Using single-cell and bulk cell RNA sequencing datasets, we found that novel X-linked immunity genes escape XCI in specific healthy human B cell subsets, and that human SLE B cells exhibit aberrant expression of X-linked genes and XIST RNA Interactome genes. Our data reveal that mislocalized XIST RNA, coupled with a dramatic reduction in heterochromatic modifications at the Xi in SLE, predispose for aberrant X-linked gene expression from the Xi, thus defining a novel genetic and epigenetic pathway that affects X-linked gene expression in human SLE B cells and likely contributes to the female-bias in SLE.

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Section: Discussionmentioning

confidence: 99%

The dynamic epigenetic regulation of the inactive X chromosome in healthy human B cells is dysregulated in lupus patients

Pyfrom

Paneru

Knoxx

et al. 2020

Preprint

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“…In human, a variant IRAK-1 haplotype with persistent increase of kinase activity was associated with a strong NF-κB activation and a severe inflammation ( 37 – 39 ). Recently, a study on cord blood cells revealed higher expression of IRAK-1 in female neonates compared to males and this was suggested as an immune advantage for females in infection-induced inflammatory diseases ( 40 ). Whether the overexpression of IRAK-1 is accompanied by an increased kinase activity was not shown in this study.…”

Section: Potential Role Of Toll-like Receptors (Tlrs) and X-linked Inmentioning

confidence: 99%

Differential Susceptibility to Infectious Respiratory Diseases between Males and Females Linked to Sex-Specific Innate Immune Inflammatory Response

et al. 2017

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It is widely acknowledged that males and females exhibit contrasting degrees of susceptibility to infectious and non-infectious inflammatory diseases. This is particularly observed in respiratory diseases where human males are more likely to be affected by infection-induced acute inflammations compared to females. The type and magnitude of the innate immune inflammatory response play a cardinal role in this sex bias. Animal models mimicking human respiratory diseases have been used to address the biological factors that could explain the distinct outcomes. In this review, we focus on our current knowledge about experimental studies investigating sex-specific differences in infection-induced respiratory diseases and we provide an update on the most important innate immune mechanisms that could explain sex bias of the inflammatory response. We also discuss whether conclusions drawn from animal studies could be relevant to human.

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“…SARS-CoV-2 infection or severity of COVID-19 is yet to be studied and understood. [156][157][158][159]…”

Section: -159mentioning

confidence: 99%

Consensus Scientific Statement on Advisory Working Guidelines and Recommendations for the Female Population in COVID-19 Era by WINCARS

Takkar

Jyotsna

Goyal

et al. 2020

Indian Journal of Cardiovascular Disease in Women WINCARS

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Expression of X-linked Toll-like receptor 4 signaling genes in female vs. male neonates

Abstract: Increased expression of IRAK1 could be responsible, in part, for sex-specific responses to infection and subsequent immune advantage in female neonates.

Cited by 23 publications

References 33 publications

The dynamic epigenetic regulation of the inactive X chromosome in healthy human B cells is dysregulated in lupus patients

The dynamic epigenetic regulation of the inactive X chromosome in healthy human B cells is dysregulated in lupus patients

Differential Susceptibility to Infectious Respiratory Diseases between Males and Females Linked to Sex-Specific Innate Immune Inflammatory Response

Consensus Scientific Statement on Advisory Working Guidelines and Recommendations for the Female Population in COVID-19 Era by WINCARS

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