Diversity of Epigenetic Features of the Inactive X-Chromosome in NK Cells, Dendritic Cells, and Macrophages

Syrett, Camille M.; Sindhava, Vishal; Sierra, Isabel; Dubin, Aimee H.; Atchison, Michael L.; Anguera, Montserrat C.

doi:10.3389/fimmu.2018.03087

Cited by 37 publications

(32 citation statements)

References 32 publications

(46 reference statements)

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“…Interestingly, cells with TLR7 escape were also more efficient at class switch recombination during naïve B cell differentiation . Another study also reported that Tlr7 was biallelically expressed in a subset of murine female pDCs . In sum, recent findings support the hypothesis that dynamic XCI maintenance and immune cell specific XCI escape contributes to immune cell sexual dimorphism, and these mechanisms may be responsible for the female disposition toward autoimmunity.…”

Section: Escape From XCImentioning

confidence: 57%

“…Indeed, we recently found evidence for diverse XCI maintenance in immune cells derived from both the lymphoid and myeloid lineages (Fig. ) . HSCs, common lymphoid progenitors (CLPs), and common myeloid progenitors (CMPs) have Xist RNA transcripts localized to the Xi, similar to fibroblasts .…”

Section: X‐chromosome Inactivation (Xci)mentioning

confidence: 96%

“…However, NK cells, myeloid and lymphoid DCs, and bone marrow‐derived macrophages (BMDMs) exhibited variable and often dispersed patterns of Xist RNA throughout their nuclei . Xist RNA was mostly enriched at the Xi in BMDMs, and these cells also displayed enrichment of H3K27me3, similar to female fibroblasts . Curiously, murine plasmacytoid DCs completely lacked detectable Xist RNA in nuclei, and had few cells with Xi‐enriched heterochromatin .…”

Section: X‐chromosome Inactivation (Xci)mentioning

confidence: 99%

“…Xist RNA was mostly enriched at the Xi in BMDMs, and these cells also displayed enrichment of H3K27me3, similar to female fibroblasts . Curiously, murine plasmacytoid DCs completely lacked detectable Xist RNA in nuclei, and had few cells with Xi‐enriched heterochromatin . The diversity with epigenetic features on the Xi among immune cells suggests that there are distinct mechanisms that maintain dosage compensation of X‐linked genes, and the molecular details of the mechanisms responsible for transcriptional silencing are unknown.…”

Section: X‐chromosome Inactivation (Xci)mentioning

confidence: 99%

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When the balance is broken: X-linked gene dosage from two X chromosomes and female-biased autoimmunity

Syrett

Anguera

2019

Journal of Leukocyte Biology

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Women and men exhibit differences in innate and adaptive immunity, and women are more susceptible to numerous autoimmune disorders. Two or more X chromosomes increases the risk for some autoimmune diseases, and increased expression of some X-linked immune genes is frequently observed in female lymphocytes from autoimmune patients. Evidence from mouse models of autoimmunity also supports the idea that increased expression of X-linked genes is a feature of female-biased autoimmunity. Recent studies have begun to elucidate the correlation between abnormal X-chromosome inactivation (XCI), an essential mechanism female somatic cells use to equalize X-linked gene dosage between the sexes, and autoimmunity in lymphocytes. In this review, we highlight research describing overexpression of X-linked immunity-related genes and female-biased autoimmunity in both humans and mouse models, and make connections with our recent work elucidating lymphocyte-specific mechanisms of XCI maintenance that become altered in lupus patients. K E Y W O R D Slupus, mouse models of lupus disease, sexual dimorphism with immune disease, X-chromosome inactivation, XCI gene escape, Xist RNA important for the development of autoimmunity, and disease results from additive effects of several risk variants, which alone would be insufficient to cause disease. Yet, hundreds of loci have been associated with autoimmune diseases, and some of these immune gene variants are present in different diseases, suggesting that common J Leukoc Biol. 2019;106:919-932.

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Section: Escape From XCImentioning

confidence: 57%

Section: X‐chromosome Inactivation (Xci)mentioning

confidence: 96%

Section: X‐chromosome Inactivation (Xci)mentioning

confidence: 99%

Section: X‐chromosome Inactivation (Xci)mentioning

confidence: 99%

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When the balance is broken: X-linked gene dosage from two X chromosomes and female-biased autoimmunity

Syrett

Anguera

2019

Journal of Leukocyte Biology

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“…The four-core genotype mouse model is an elegant tool to study the effect of X/Y-linked genes, especially in gonadectomised mice. However, extrapolation of results from mouse models to humans is complicated as the regulation of XCI differs between mice and humans [50,51].…”

Section: Discussionmentioning

confidence: 99%

SeXY chromosomes and the immune system: reflections after a comparative study

et al. 2020

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Background: Sex bias in immune function has been contributed in part to a preponderance of immune systemrelated genes (ISRG) on the X-chromosome. We verified whether ISRG are more abundant on the X chromosome as compared to autosomal chromosomes and reflected on the impact of our findings. Methods: Consulting freely accessible databases, we performed a comparative study consisting of three complementary strategies. First, among coding X/Y-linked genes, the abundance of ISRG was compared to the abundance of genes dedicated to other systems. Genes were assigned considering three criteria: disease, tissue expression, and function (DEF approach). In addition, we carried out two genome-wide approaches to compare the contribution of sex and autosomal chromosomes to immune genes defined by an elevated expression in lymphatic tissues (LTEEG approach) or annotation to an immune system process, GO:0002376 (GO approach).Results: The X chromosome had less immune genes than the median of the autosomal chromosomes. Among Xlinked genes, ISRG ranked fourth after the reproductive and nervous systems and genes dedicated to development, proliferation and apoptosis. On the Y chromosome, ISRG ranked second, and at the pseudoautosomal region (PAR) first. According to studies on the expression of X-linked genes in a variety of (mostly non-lymphatic) tissues, almost two-thirds of ISRG are expressed without sex bias, and the remaining ISRG presented female and male bias with similar frequency. Various epigenetic controllers, X-linked MSL3 and Y-linked KDM5D and UTY, were preferentially expressed in leukocytes and deserve further attention for a possible role in sex biased expression or its neutralisation. Conclusions: The X chromosome is not enriched for ISRG, though particular X-linked genes may be responsible for sex differences in certain immune responses. So far, there is insufficient information on sex-biased expression of X/ Y-linked ISRG in leukocytes to draw general conclusions on the impact of X/Y-linked ISRG in immune function. More research on the regulation of the expression X-linked genes is required with attention to 1) female and male mechanisms that may either augment or diminish sex biased expression and 2) tissue-specific expression studies.

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Genetics of Sex Differences in Immunity

Gal-Oz,

Shay

2023

Current Topics in Microbiology and Immunology

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Diversity of Epigenetic Features of the Inactive X-Chromosome in NK Cells, Dendritic Cells, and Macrophages

Cited by 37 publications

References 32 publications

When the balance is broken: X-linked gene dosage from two X chromosomes and female-biased autoimmunity

When the balance is broken: X-linked gene dosage from two X chromosomes and female-biased autoimmunity

SeXY chromosomes and the immune system: reflections after a comparative study

Genetics of Sex Differences in Immunity

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