Fine-tuning SLE treatment: the potential of selective TYK2 inhibition DOI Creative Commons
Yurie Satoh, Shingo Nakayamada, Yoshiya Tanaka

et al.

RMD Open, Journal Year: 2024, Volume and Issue: 10(4), P. e005072 - e005072

Published: Dec. 1, 2024

In systemic lupus erythematosus (SLE), adaptive immunity is activated by the stimulation of innate immunity, leading to development autoreactive T cells and activation differentiation B cells. Cytokine signalling plays an essential role in pathogenesis progression this disease. particular, function CD4+ cell subsets, which play a central SLE pathology, are significantly altered cytokine stimulation. Many cytokines transmit signals via Janus-activated kinase (JAK)-STAT pathway, but there no one-to-one correspondence between receptors JAK/TYK2. Multiple activate JAK/TYK2, multiple JAK/TYK2 molecules simultaneously single cytokine. Therefore, modulation JAK-STAT pathway has potential control immune responses SLE. Although several inhibitors currently undergoing clinical trials, more selective drugs that can target according specific pathology disease required. TYK2 inhibitors, involved signal transduction type I interferon interleukin-12/23 pathways linked susceptibility genes SLE, may have fine-tune cells, particularly

Language: Английский

RNA sensing at the crossroads of autoimmunity and autoinflammation DOI Open Access
Sandra G. Williams, Soyeong Sim, Sandra L. Wolin

et al.

RNA, Journal Year: 2025, Volume and Issue: unknown, P. rna.080304.124 - rna.080304.124

Published: Jan. 8, 2025

Immune-mediated diseases are common in humans. The immune system is a complex host defense that evolved to protect us from pathogens, but also plays an important role homeostatic processes, removing dead or senescent cells, and participating tumor surveillance. human has two arms: the older innate system, newer adaptive system. Sensing of foreign RNA critical system’s ability recognize especially viral infections. However, sensors strongly implicated autoimmune autoinflammatory diseases, highlighting importance balancing pathogen recognition with tolerance RNAs can resemble their counterparts. We describe how bind ligands, this binding coupled upregulation Type I interferon-stimulated genes, ways which mutations genes play roles homeostasis have been linked diseases.

Language: Английский

Citations

0
Rare and common single nucleotide variants in childhood-onset systemic lupus erythematosus DOI Creative Commons

Ahmed Sayadi,

Johanna K. Sandling, Maija‐Leena Eloranta

et al.

Lupus Science & Medicine, Journal Year: 2025, Volume and Issue: 12(1), P. e001436 - e001436

Published: Feb. 1, 2025

Background SLE is a systemic autoimmune disease with large number of common risk gene variants, but several rare variants can cause monogenic SLE. The relationship between and in unclear. We therefore investigated the occurrence deleterious patients childhood-onset (cSLE) adult-onset (aSLE) compared frequency these their individual polygenic score (PRS). Materials methods Targeted sequencing 1832 regions, including coding regions 31 genes associated SLE, was performed 958 1026 healthy individuals. A total 116 had onset before age 18 (cSLE). An variant PRS created from 37 genome-wide association study single nucleotide (SNVs). Results Rare SNVs (RD SNVs) were observed 23 SLE-associated genes. Six per cent cSLE, 3.2% controls 4.6% aSLE, carried alleles. In RD C1S , DDX58 IFIH1 IKZF1 RNASEH2A C8A analysis showed that cSLE any similar average as control Conclusion small proportion carriers to individuals, suggesting importance heterozygous driving subset children

Language: Английский

Citations

0
Association of TNFAIP3 expression and gene polymorphisms with systemic lupus erythematosus susceptibility in the Chinese Han population DOI
Qiuyu Yang, Guangliang Wei,

Zhou Xi-ping

et al.

Human Immunology, Journal Year: 2025, Volume and Issue: 86(3), P. 111288 - 111288

Published: March 15, 2025

Language: Английский

Citations

0
Trans-eQTL mapping prioritisesUSP18as a negative regulator of interferon response at a lupus risk locus DOI Creative Commons

Krista Freimann,

Anneke Brümmer, Robert Warmerdam

et al.

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

Published: July 16, 2024

Abstract Although genome-wide association studies have provided valuable insights into the genetic basis of complex traits and diseases, translating these findings to causal genes their downstream mechanisms remains challenging. We performed trans expression quantitative trait locus ( -eQTL) meta-analysis in 3,734 lymphoblastoid cell line samples, identifying four robust loci that replicated an independent multi-ethnic dataset 682 individuals. prioritised a missense variant ubiquitin specific peptidase 18 USP18) gene is known negative regulator interferon signalling has previously been associated with increased risk systemic lupus erythematosus (SLE). The SLE allele 50 interferon-inducible genes, suggesting impairs USP18’s ability effectively limit response. Intriguingly, USP18 -eQTL signal would not discovered up 43,301 whole blood reaffirming importance capturing context-specific effects for GWAS interpretation.

Language: Английский

Citations

1
Could tolerance to DNA be broken in the gut in systemic lupus erythematosus? DOI Creative Commons
Jo Spencer, Sahil Jain

Immunology Letters, Journal Year: 2024, Volume and Issue: 270, P. 106937 - 106937

Published: Oct. 28, 2024

Language: Английский

Citations

0
Mapping integral cell-type-specific interferon-induced gene regulatory networks (GRNs) involved in systemic lupus erythematosus using systems and computational analysis DOI Creative Commons

Blessy Kiruba,

Akshayata Naidu,

Vino Sundararajan

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 11(1), P. e41342 - e41342

Published: Dec. 19, 2024

Language: Английский

Citations

0
Fine-tuning SLE treatment: the potential of selective TYK2 inhibition DOI Creative Commons
Yurie Satoh, Shingo Nakayamada, Yoshiya Tanaka

et al.

RMD Open, Journal Year: 2024, Volume and Issue: 10(4), P. e005072 - e005072

Published: Dec. 1, 2024

In systemic lupus erythematosus (SLE), adaptive immunity is activated by the stimulation of innate immunity, leading to development autoreactive T cells and activation differentiation B cells. Cytokine signalling plays an essential role in pathogenesis progression this disease. particular, function CD4+ cell subsets, which play a central SLE pathology, are significantly altered cytokine stimulation. Many cytokines transmit signals via Janus-activated kinase (JAK)-STAT pathway, but there no one-to-one correspondence between receptors JAK/TYK2. Multiple activate JAK/TYK2, multiple JAK/TYK2 molecules simultaneously single cytokine. Therefore, modulation JAK-STAT pathway has potential control immune responses SLE. Although several inhibitors currently undergoing clinical trials, more selective drugs that can target according specific pathology disease required. TYK2 inhibitors, involved signal transduction type I interferon interleukin-12/23 pathways linked susceptibility genes SLE, may have fine-tune cells, particularly

Language: Английский

Citations

0