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

et al.

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

Published: Dec. 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.

Language: Английский

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

The Journal of Experimental Medicine, Journal Year: 2025, Volume and Issue: 222(3)

Published: Jan. 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.

Language: Английский

Citations

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, Journal Year: 2025, Volume and Issue: 93, P. 102543 - 102543

Published: Feb. 27, 2025

Language: Английский

Citations

0
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, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

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

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: March 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.

Language: Английский

Citations

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

et al.

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

Published: April 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.

Language: Английский

Citations

0
Der große Unterschied DOI

Michael Groß

Nachrichten aus der Chemie, Journal Year: 2025, Volume and Issue: 73(5), P. 77 - 79

Published: April 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.

Citations

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

et al.

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

Published: Dec. 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.

Language: Английский

Citations

1