Journal of Translational Autoimmunity, Год журнала: 2024, Номер 9, С. 100252 - 100252
Опубликована: Окт. 9, 2024
Journal of Clinical Investigation, Год журнала: 2024, Номер 134(18)
Опубликована: Сен. 16, 2024
Autoimmune diseases are a leading cause of disability worldwide. Most autoimmune occur more often in women than men, with rheumatic being among those most highly expressed women. Several key factors, identified mainly animal models and cell culture experiments, important increasing disease females. These include sex hormones, immune genes including found on the X chromosome, sex-specific epigenetic effects by estrogen environment, regulation messenger RNA microRNAs extracellular vesicles. Evidence is also emerging that viruses as well drugs or toxins damage mitochondria may contribute to increased levels autoantibodies against nuclear mitochondrial antigens, which common many diseases. The purpose this Review summarize our current understanding mechanisms determine differences disease.
Язык: Английский
Процитировано
11
The Journal of Experimental Medicine, Год журнала: 2025, Номер 222(4)
Опубликована: Март 6, 2025
Sex differences in immunity are well-documented, though mechanisms underpinning these remain ill-defined. Here, a human-only ex vivo study, we demonstrate that postpubertal cisgender females have higher levels of CD19+CD27+IgD− class-switched memory B cells compared with age-matched males. This increase is only observed after puberty and before menopause, suggesting strong influence for sex hormones. Accordingly, express high estrogen receptor 2 (ESR2), class-switch–regulating genes enriched ESR2-binding sites. In gender-diverse cohort, blockade natal transgender males (XX karyotype) reduced cell frequency, while gender-affirming estradiol treatment (XY did not levels. postmenopausal cis-females, were increased those taking hormone replacement therapy (HRT) who not. These data hormones chromosomes work tandem to impact immune responses, influencing the frequency individuals an XX chromosomal background.
Язык: Английский
Процитировано
2
Science, Год журнала: 2024, Номер 386(6725)
Опубликована: Ноя. 28, 2024
Alzheimer’s disease (AD) and other age-related disorders associated with demyelination exhibit sex differences. In this work, we used single-nuclei transcriptomics to dissect the contributions of chromosomes gonads in AD. a mouse model demyelination, identified roles modifying microglia oligodendrocyte responses before after myelin loss. an AD-related expressing APOE4, XY heightened interferon (IFN) response tau-induced demyelination. The X-linked gene, Toll-like receptor 7 ( Tlr7 ), regulated sex-specific IFN myelin. Deletion dampened differences while protecting against Administering TLR7 inhibitor mitigated motor impairment male mice, indicating that plays role male-biased type I Interferon aging-
Язык: Английский
Процитировано
7
The Journal of Experimental Medicine, Год журнала: 2024, Номер 222(3)
Опубликована: Дек. 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
Язык: Английский
Процитировано
7
The Journal of Experimental Medicine, Год журнала: 2025, Номер 222(3)
Опубликована: Янв. 17, 2025
Systemic sclerosis (SSc) is a debilitating autoimmune disease that preferentially afflicts women. The molecular origins of this female bias are unclear. A new study plasmacytoid dendritic cells from SSc patients by Du et al. (https://doi.org/10.1084/jem.20231809) suggests the X chromosome may play key role.
Язык: Английский
Процитировано
1
Clinical Reviews in Allergy & Immunology, Год журнала: 2025, Номер 68(1)
Опубликована: Фев. 17, 2025
Abstract As a heterogeneous B cell subset, age-associated cells (ABCs) exhibit distinct transcription profiles, extrafollicular differentiation processes, and multiple functions in autoimmunity. TLR7 TLR9 signals, along with IFN-γ IL-21 stimulation, are both essential for ABC differentiation, which is also regulated by chemokine receptors including CXCR3 CCR2 integrins CD11b CD11c. Given their antigen uptake presentation, autoantibody proinflammatory cytokine secretion, T helper activation, ABCs display potential the prognosis, diagnosis, therapy autoimmune diseases, systemic lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome, sclerosis, neuromyelitis optica spectrum disorders, ankylosing spondylitis. Specifically targeting inhibiting T-bet CD11c activating ARA2 represents therapeutic strategies SLE RA. Although single-cell sequencing technologies have recently revealed characteristics of ABCs, further investigations to explore validate ABC-target therapies still warranted.
Язык: Английский
Процитировано
1
Nature Aging, Год журнала: 2025, Номер unknown
Опубликована: Май 1, 2025
Язык: Английский
Процитировано
1
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Май 18, 2024
Systemic lupus erythematosus (SLE) is an autoimmune disease preferentially observed in females. X-linked gene expression XX females normalized to that of XY males by X-Chromosome Inactivation (XCI). However, B cells from female SLE patients and mouse models exhibit mislocalization Xist RNA, a critical regulator XCI, aberrant genes, suggesting impairment XCI may contribute disease. Here, we find subset mice harboring conditional deletion
Язык: Английский
Процитировано
6
Frontiers in Bioscience-Landmark, Год журнала: 2025, Номер 30(1)
Опубликована: Янв. 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.
Язык: Английский
Процитировано
0
Leukemia, Год журнала: 2025, Номер unknown
Опубликована: Янв. 26, 2025
In addition to biological factors, maternal exposures during pregnancy can contribute leukemogenesis in offspring. We conducted a population-based cohort study Sweden investigate the association between risk of acute lymphoblastic leukemia (ALL) offspring and anthropometrics pregnancy. A total 2,961,435 live-born singletons 1983-2018 were followed from birth ALL diagnosis, end age 18, or 2018. 1388 children diagnosed with (55.6% boys). observed an increased among daughters overweight/obese mothers early [Body mass index (BMI) ≥ 25 kg/m2; Standardized incidence ratio (SIR) = 1.4, 95% CI: 1.2-1.6] compared normal BMI. This was not found their sons (SIR 1.0, 0.9-1.1). Similar results for BMI before delivery. did find low high gestational weight gain (GWG) (both SIRs 1.0) male/female These suggest that overweight/obesity are important factors childhood daughters, whereas GWG is associated ALL. Further research on this mother-daughter may shed light possible sex hormone/chromosome-related etiology
Язык: Английский
Процитировано
0