Human monocyte subtype expression of neuroinflammation and regeneration-related genes is linked to age and sex DOI Creative Commons

Juliane F. Tampé,

Emanuela Monni,

Sara Palma-Tortosa

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 13, 2024

ABSTRACT Stroke is a leading cause of disability and the third death. The immune system plays an essential role in post-stroke recovery. After ischemic stroke, monocytes infiltrate injured brain tissue can exacerbate or mitigate damage. Ischemic stroke more prevalent aged population, aging exhibits altered response. There are also sex disparities incidence, outcomes, recovery, these differences may be hormone-driven determined by genetic epigenetic factors. Here, we studied whether human peripheral blood monocyte subtype (classical, intermediate, non-classical) expression neuronal inflammation- regeneration-related genes depends on age sex. A FACS analysis samples from 44 volunteers (male female, 28 to 98) showed that contrast other cells, proportion natural killer cells increased females. B-cells decreased both sexes with age, subtypes were not linked Gene qPCR identified several differentially correlating within different subtypes. Interestingly, ANXA1 CD36 consistent increase all monocytes, specifically intermediate ( ) non-classical Other IL-1β, S100A8, TNFα, CD64, CD33, TGFβ1, TLR8, CD91 changed aging. Most age-dependent gene changes expressed female monocytes. Our data shed light nuanced interplay shaping distinct Understanding dynamics could pave way for targeted interventions personalized approaches care, particularly population individuals sexes.

Language: Английский

Altered X-chromosome inactivation predisposes to autoimmunity DOI Creative Commons
Christophe Huret, Léa Ferrayé,

Antoine David

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(18)

Published: May 3, 2024

In mammals, males and females show marked differences in immune responses. Males are globally more sensitive to infectious diseases, while susceptible systemic autoimmunity. X-chromosome inactivation (XCI), the epigenetic mechanism ensuring silencing of one X females, may participate these sex biases. We perturbed expression trigger XCI, noncoding RNA Xist , female mice. This resulted reactivation genes on inactive X, including members Toll-like receptor 7 (TLR7) signaling pathway, monocyte/macrophages dendritic B cells. Consequently, mice spontaneously developed inflammatory signs typical lupus, anti–nucleic acid autoantibodies, increased frequencies age-associated germinal center cells, expansion Mechanistically, TLR7 is dysregulated macrophages, leading sustained target upon stimulation. These findings provide a direct link between maintenance XCI female-biased autoimmune manifestations highlight altered as cause

Language: Английский

Citations

30
Comprehensive review for non-coding RNAs: From mechanisms to therapeutic applications DOI
Yanjun Zhang,

Lijuan Zhan,

Xue Jiang

et al.

Biochemical Pharmacology, Journal Year: 2024, Volume and Issue: 224, P. 116218 - 116218

Published: April 21, 2024

Language: Английский

Citations

16
Small RNA and Toll-like receptor interactions: origins and disease mechanisms DOI
Jiancheng Yu, Xu Dong Zhang, Chen Cai

et al.

Trends in Biochemical Sciences, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

1
Modulation of plasmacytoid dendritic cells response in inflammation and autoimmunity DOI
Marie Dominique Ah Kioon, Paôline Laurent, Vidyanath Chaudhary

et al.

Immunological Reviews, Journal Year: 2024, Volume and Issue: 323(1), P. 241 - 256

Published: March 29, 2024

Summary The discovery of toll‐like receptors (TLRs) and the subsequent recognition that endogenous nucleic acids (NAs) could serve as TLR ligands have led to essential insights into mechanisms healthy immune responses well pathogenic relevant systemic autoimmune inflammatory diseases. In lupus erythematosus, sclerosis, rheumatoid arthritis, NA‐containing complexes ligands, with distinct implications depending on additional stimuli available. Plasmacytoid dendritic cells (pDCs), robust producers type I interferon (IFN‐I), are providing critical TLR‐mediated tissue repair, generation inflammation, autoimmunity fibrosis, processes central pathogenesis many this review, we describe recent data characterizing role platelets NA‐binding chemokines in modulation signaling pDCs, for how IFN‐I products pDCs contribute inflammation wound healing by monocyte/macrophages. Chemokine modulators B cell tolerance interactions between metabolic pathways also considered. their contribution diseases suggest new opportunities identification novel therapeutic targets.

Language: Английский

Citations

9
Altered X-chromosome inactivation of the TLR7/8 locus and heterogeneity of pDCs in systemic sclerosis DOI
Yong Du, Bérénice Faz-Lopez, Marie Dominique Ah Kioon

et al.

The Journal of Experimental Medicine, Journal Year: 2024, Volume and Issue: 222(3)

Published: Dec. 13, 2024

Systemic sclerosis (SSc) is an autoimmune disease that has a strong female predominance. Both the X-linked TLR7 and TLR8 can induce type I IFN (IFN-I) by plasmacytoid DCs (pDCs), which promote fibrosis. We identified five subclusters of pDCs, including ISGhigh clusters were over-represented in SSc patients. observed both genes escape from X chromosome inactivation (XCI) at higher frequency pDCs patients, was associated with changes protein profile. Combined DNA/RNA FISH analysis revealed TLR7/8 locus preferentially located outside inactive (Xi) territory when expressed, suggesting higher-order loop formation linked to expression Xi. Furthermore, levels XIST transcriptional repressor SPEN reduced pDCs. Hence, our data heterogeneity suggested altered XCI may contribute chronic IFN-I activity

Language: Английский

Citations

9
Human and Murine Toll-like Receptor-Driven Disease in Systemic Lupus Erythematosus DOI Open Access
Susannah von Hofsten, Kristin Andreassen Fenton, Hege Lynum Pedersen

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(10), P. 5351 - 5351

Published: May 14, 2024

The pathogenesis of systemic lupus erythematosus (SLE) is linked to the differential roles toll-like receptors (TLRs), particularly TLR7, TLR8, and TLR9. TLR7 overexpression or gene duplication, as seen with Y-linked autoimmune accelerator (Yaa) locus agonist imiquimod, correlates increased SLE severity, specific polymorphisms gain-of-function variants are associated enhanced susceptibility severity. In addition, X-chromosome location its escape from inactivation provide a genetic basis for female predominance in SLE. absence TLR8 TLR9 have been shown exacerbate detrimental effects leading upregulated activity disease severity mouse models regulatory functions proposed involve competition endosomal trafficking chaperone UNC93B1. However, recent evidence implies more direct, on activity. association between age-associated B cells (ABCs) autoantibody production positions these potential targets treatment SLE, but lack markers necessitates further research precise therapeutic intervention. Therapeutically, targeting TLRs promising strategy treatment, drugs like hydroxychloroquine already clinical use.

Language: Английский

Citations

8
Aging promotes reactivation of the Barr body at distal chromosome regions DOI Creative Commons
Sarah Hoelzl, Tim P. Hasenbein, Stefan Engelhardt

et al.

Nature Aging, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Language: Английский

Citations

1
Common and distinct metabolomic markers related to immune aging in Western European and East African populations DOI Creative Commons
Özlem Bulut, Godfrey S. Temba, Valerie A. C. M. Koeken

et al.

Mechanisms of Ageing and Development, Journal Year: 2024, Volume and Issue: 218, P. 111916 - 111916

Published: Feb. 14, 2024

In old age, impaired immunity causes high susceptibility to infections and cancer, higher morbidity mortality, poorer vaccination efficiency. Many factors, such as genetics, diet, lifestyle, impact aging. This study aimed investigate how immune responses change with age in healthy Dutch Tanzanian individuals identify common metabolites associated an aged profile. We performed untargeted metabolomics from plasma age-associated metabolites, we correlated their concentrations ex-vivo cytokine production by cells, DNA methylation-based epigenetic aging, telomere length. Innate were impacted differently cohorts. Age-related decline steroid hormone precursors both populations was systemic inflammation lower responses. Hippurate 2-phenylacetamide, commonly more abundant older individuals, negatively length positively Lastly, identified several that might contribute the stronger innate Tanzanians. The shared metabolomic signatures of two cohorts suggest mechanisms revealing potential contributions. These findings also reflect genetic or environmental effects on circulating modulate

Language: Английский

Citations

4
Ignoring Gender-Based Immunometabolic Reprograming, a Risky Business in Immune-Based Precision Medicine DOI Creative Commons
Vijay Kumar

Frontiers in Bioscience-Landmark, Journal Year: 2025, Volume and Issue: 30(1)

Published: Jan. 9, 2025

Immunology advances have increased our understanding of autoimmune, auto-inflammatory, immunodeficiency, infectious, and other immune-mediated inflammatory diseases (IMIDs). Furthermore, evidence is growing for the immune involvement in aging, metabolic neurodegenerative diseases, different cancers. However, further research has indicated sex/gender-based differences, which increase higher incidences various autoimmune (AIDs), such as systemic lupus erythematosus (SLE), myasthenia gravis, rheumatoid arthritis (RA) females. On hand, reproductive-age females also show a more potent response against infections vaccines than their age-matched males—furthermore, some immune-based therapies, including checkpoint inhibitors (ICIs), gender-based efficacy adverse events. Metabolic demands are males Immune cell function polarization governed by reprogramming, called immunometabolism immunometabolic reprogramming (IR). Therefore, sex/gender-associated differences therapeutics indicate demand IR studies to precision medicine.

Language: Английский

Citations

0
Sexual dimorphism in immunity and longevity among the oldest old DOI Creative Commons

Nelli A. Arakelyan,

D. A. Kupriyanova,

Jeļena Vasiļevska

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 17, 2025

Human longevity is a sex-biased process in which sex chromosomes and sex-specific immunity may play crucial role the health lifespan disparities between men women. Generally, women have higher life expectancy than men, exhibiting lower infection rates for broad range of pathogens, results prevalence female centenarians compared to males. Investigation immunological changes that occur during healthy aging, while taking into account differences sexes, can significantly enhance our understanding mechanisms underlie longevity. In this review, we aim summarize current knowledge on sexual dimorphism human immune system gut microbiome with particular focus centenarians, based exclusively data.

Language: Английский

Citations

0