Mechanosensing regulates pDC activation in the skin through NRF2 activation DOI
Vidyanath Chaudhary, Bikash Mishra, Marie Dominique Ah Kioon

и другие.

The Journal of Experimental Medicine, Год журнала: 2024, Номер 222(3)

Опубликована: Дек. 13, 2024

Plasmacytoid DCs (pDCs) infiltrate the skin, chronically produce type I interferon (IFN-I), and promote skin lesions fibrosis in autoimmune patients. However, what controls their activation is unknown. Here, we report that increased stiffness inhibits production of IFN-I by pDCs. Mechanistically, mechanosensing activates stress pathways including NRF2, which induces pentose phosphate pathway reduces pyruvate levels, a product necessary for pDC responses. Modulating NRF2 activity vivo controlled response, leading to resolution or chronic induction skin. In systemic sclerosis (SSc) patients, although was induced skin-infiltrating pDCs, as compared with blood IFN response maintained. We observed CXCL4, profibrotic chemokine elevated fibrotic able overcome stiffness-mediated inhibition, allowing responses pDCs Hence, these data identify novel regulatory mechanism exerted microenvironment points dysregulation this patients inflammation fibrosis.

Язык: Английский

pDCs, type 1 IFN, and the female predileXion of SSc DOI Open Access
Nikhil Jiwrajka, Montserrat C. Anguera

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
More X’s, more problems: how contributions from the X chromosomes enhance female predisposition for autoimmunity DOI
Claudia D. Lovell, Montserrat C. Anguera

Current Opinion in Immunology, Год журнала: 2025, Номер 93, С. 102543 - 102543

Опубликована: Фев. 27, 2025

Язык: Английский

Процитировано

1
Immuno’logique (l’actualité scientifique que vous n’auriez pas osé lire ailleurs) : chromosome X, Xist et auto-immunité féminine DOI
Valentin Lacombe

La Revue de Médecine Interne, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
Oxidative damage reprograms the Hippo-WNT network via X-linked Kdm6a to activate blastocyst dormancy and prevent offspring tumorigenesis. DOI Creative Commons
Zhen Li, Yue Huang, Siyao Ha

и другие.

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Март 24, 2025

Abstract In vitro fertilization (IVF) has been associated with an increased risk of tumorigenesis in offspring. Our previous research indicated that oxidative damage-induced X-chromosome aneuploidy (XCA) IVF mouse embryos may contribute to However, the tumorigenic mechanisms underlying this phenomenon remain unclear. The present study elucidates elevated number X chromosomes leads excessive transcription Xist, resulting aberrant inactivation (XCI). This abnormal XCI subsequently inhibits expression X-linked lysine demethylase 6A (Kdm6a), which is followed by increase repressive marker H3K27me3 and a decrease active markers H3K27ac/H3K4me3. To investigate epigenetic involved offspring tumorigenesis, we employed CUT&Tag technology map genome-wide profiles H3K27ac/H3K4me3/H3K27me3 blastocysts. We found Kdm6a-dependent histone modifications exhibited close relationship leukemia regulating cancer pathways, particularly Hippo/Yap1 Wnt (Wnt/β-catenin Wnt/RhoA) signalings oxidatively damaged embryos. Kdm6a plasmid antioxidant EGCG were maintain stability antagonize effects ROS on Hippo pathways. concluded loss participated via oncogenic RhoA/β-catenin activation tumor-suppressive during IVF. or hepatic tumors was not derived from further analysis revealed play crucial role pluripotency embryonic stem cells. antagonized formation rosette-like structures naive gene Oct4 as well primed Otx2 implies essentail for naive-to-primed transition blastocysts implantation. hypothesize adversely affects blastocyst implantation, thereby prevent birth tumorigenesis.

Язык: Английский

Процитировано

0
A review of recent studies on the pathogenesis of Systemic Sclerosis: focus on fibrosis pathways DOI Creative Commons
Sergio A. Jiménez,

Fabian A. Mendoza,

Sonsoles Piera‐Velazquez

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Апрель 16, 2025

Systemic Sclerosis (SSc) is a systemic autoimmune disease of unknown etiology characterized by the development frequently progressive cutaneous and internal organ fibrosis accompanied severe vascular alterations. The pathogenesis SSc highly complex and, despite extensive investigation, has not been fully elucidated. Numerous studies have suggested that etiologic factors cause multiple alterations in genetically receptive hosts, leading to progression. These events may be functionally pathologically interconnected include: 1) Structural functional microvascular endothelial cell abnormalities; 2) Severe oxidative stress high reactive oxygen species (3); Frequently visceral fibrosis; 4) Transdifferentiation various types into activated myofibroblasts, cells ultimately responsible for fibrotic process; 5) Establishment chronic inflammatory process affected tissues; 6) Release cytokines, chemokines, growth from cells; 7) Abnormalities humoral cellular immunity with production specific autoantibodies; 8) Epigenetic including changes non-coding RNAs. manifest different levels intensity organs display remarkable individual variability, resulting wide heterogeneity extent severity clinical manifestations. Here, we will review some recent related pathogenesis.

Язык: Английский

Процитировано

0
Der große Unterschied DOI

Michael Groß

Nachrichten aus der Chemie, Год журнала: 2025, Номер 73(5), С. 77 - 79

Опубликована: Апрель 30, 2025

Abstract Geschlechter‐Unterschiede sind in der Medizin relevant, etwa im Immunsystem, bei Herzinfarkten und Wirkung von Medikamenten. Und sie zu lange vernachlässigt worden. Es bleibt noch einiges verbessern, bis jede:r die richtige Behandlung bekommt.

Процитировано

0
The Inactive X Chromosome: A Genetic Driver of Female‐Biased Rheumatic Autoimmune Disorders? DOI Creative Commons
Léa Ferrayé,

Mélissa Nieucel,

Magali Savignac

и другие.

European Journal of Immunology, Год журнала: 2025, Номер 55(5)

Опубликована: Май 1, 2025

ABSTRACT Females have a better ability to resolve infections compared males, but also greater susceptibility develop autoimmunity. Besides the initial interest in contribution of sex‐steroid hormone signaling, role genetic factors linked X chromosome has recently received much attention. In humans and mice, number chromosomes, rather than hormones, is associated with higher risk autoimmunity, particularly rheumatic diseases, such as SLE, Sjögren's syndrome, or systemic sclerosis. this review, we will summarize recent advances various mechanisms pathways involving female sex‐biased autoimmune diseases. We focus on experimental evidence suggesting that expression X‐linked genes due dysregulation inactivation maintenance could contribute predisposition for autoautoimmunity.

Язык: Английский

Процитировано

0
Sex Bias in Systemic Sclerosis: from Clinical to Immunological Differences DOI Creative Commons
Lazaros I. Sakkas, Dimitrios P. Bogdanos, Ian C. Chikanza

и другие.

Clinical Reviews in Allergy & Immunology, Год журнала: 2025, Номер 68(1)

Опубликована: Май 27, 2025

Язык: Английский

Процитировано

0
Mechanosensing regulates pDC activation in the skin through NRF2 activation DOI
Vidyanath Chaudhary, Bikash Mishra, Marie Dominique Ah Kioon

и другие.

The Journal of Experimental Medicine, Год журнала: 2024, Номер 222(3)

Опубликована: Дек. 13, 2024

Plasmacytoid DCs (pDCs) infiltrate the skin, chronically produce type I interferon (IFN-I), and promote skin lesions fibrosis in autoimmune patients. However, what controls their activation is unknown. Here, we report that increased stiffness inhibits production of IFN-I by pDCs. Mechanistically, mechanosensing activates stress pathways including NRF2, which induces pentose phosphate pathway reduces pyruvate levels, a product necessary for pDC responses. Modulating NRF2 activity vivo controlled response, leading to resolution or chronic induction skin. In systemic sclerosis (SSc) patients, although was induced skin-infiltrating pDCs, as compared with blood IFN response maintained. We observed CXCL4, profibrotic chemokine elevated fibrotic able overcome stiffness-mediated inhibition, allowing responses pDCs Hence, these data identify novel regulatory mechanism exerted microenvironment points dysregulation this patients inflammation fibrosis.

Язык: Английский

Процитировано

1