Immune Imbalance in Primary Membranous Nephropathy at Single-cell Resolution DOI Creative Commons

Xuan Tie,

Z Chen,

Shulei Yao

et al.

Frontiers in Bioscience-Landmark, Journal Year: 2025, Volume and Issue: 30(2)

Published: Feb. 24, 2025

Primary membranous nephropathy (pMN) often progresses to end-stage renal disease (ESRD) in the absence of immunosuppressive therapy. The immunological mechanisms driving pMN progression remain insufficiently understood. We developed a single-cell transcriptomic profile peripheral blood mononuclear cells (PBMCs) from 11 newly-diagnosed patients and 5 healthy donors. Through correlation analysis, we identified potential biomarkers for stratification poor prognosis. Expression levels several proinflammatory factors were significantly increased compared donors, such as interleukins (IL1B, IL8, IL15) interferon G (IFNG). Multiple pattern recognition receptors involved signaling also upregulated patients, including NOD-like (NLRs) (NLRP1, NLRP3, NLRC5), RNA helicases (DDX58, IFIH1, DHX9, DHX36), cGAS (cyclic GMP-AMP synthase) IFI16 (interferon gamma inducible protein 16). Additionally, human leukocyte antigen molecules HLA-DQA1 HLA-DRB1 enriched memory B patients. More importantly, found that genes antiviral defense response elevated high-risk relative low-risk group. than twenty negatively correlated with estimated glomerular filtration rate (eGFR), BST2 (bone marrow stromal cell 2) SLC35F1 (solute carrier family 35 member F1). Their predicted values confirmed larger population nephrotic syndrome or other chronic kidney diseases public database. Furthermore, series scoring systems distinguishing low- moderate-risk individuals. Our study provides insight into mechanism identifies numerous pathways therapeutic targets managing pMN.

Language: Английский

Molecular mimicry and autoimmunity in the time of COVID-19 DOI
Manuel Rojas,

María Herrán,

Carolina Ramírez‐Santana

et al.

Journal of Autoimmunity, Journal Year: 2023, Volume and Issue: 139, P. 103070 - 103070

Published: June 12, 2023

Language: Английский

Citations

40
Epigenetic regulation of B cells and its role in autoimmune pathogenesis DOI Creative Commons
Fan Xiao, Ke Rui, Xiaofei Shi

et al.

Cellular and Molecular Immunology, Journal Year: 2022, Volume and Issue: 19(11), P. 1215 - 1234

Published: Oct. 12, 2022

Abstract B cells play a pivotal role in the pathogenesis of autoimmune diseases. Although previous studies have shown many genetic polymorphisms associated with B-cell activation patients various disorders, progress epigenetic research has revealed new mechanisms leading to hyperactivation. Epigenetic mechanisms, including those involving histone modifications, DNA methylation, and noncoding RNAs, regulate responses, their dysregulation can contribute Patients diseases show alterations that lead initiation perpetuation inflammation. Moreover, clinical animal model promising potential therapies for patients. In this review, we present an up-to-date overview focus on roles regulating functional subsets. Furthermore, discuss highlight its contribution development Based preclinical evidence, novel biomarkers disorders.

Language: Английский

Citations

39
Genetics of SLE: mechanistic insights from monogenic disease and disease-associated variants DOI
Carola G. Vinuesa, Nan Shen, Thuvaraka Ware

et al.

Nature Reviews Nephrology, Journal Year: 2023, Volume and Issue: 19(9), P. 558 - 572

Published: July 12, 2023

Language: Английский

Citations

39
Systemic lupus erythematosus: latest insight into etiopathogenesis DOI Open Access

Akhil Akhil,

Rohit Bansal, Kumari Anupam

et al.

Rheumatology International, Journal Year: 2023, Volume and Issue: 43(8), P. 1381 - 1393

Published: May 24, 2023

Language: Английский

Citations

32
Suppression of cytokine release syndrome during CAR-T-cell therapy via a subcutaneously injected interleukin-6-adsorbing hydrogel DOI
Xianlei Li, Ningqiang Gong, Falin Tian

et al.

Nature Biomedical Engineering, Journal Year: 2023, Volume and Issue: 7(9), P. 1129 - 1141

Published: Sept. 11, 2023

Language: Английский

Citations

32
Influence of X chromosome in sex-biased autoimmune diseases DOI Creative Commons

Charles‐Henry Miquel,

Bérénice Faz-Lopez, Jean‐Charles Guéry

et al.

Journal of Autoimmunity, Journal Year: 2023, Volume and Issue: 137, P. 102992 - 102992

Published: Jan. 12, 2023

Language: Английский

Citations

30
Innate virus-sensing pathways in B cell systemic autoimmunity DOI
Carola G. Vinuesa, Amalie Grenov, George Kassiotis

et al.

Science, Journal Year: 2023, Volume and Issue: 380(6644), P. 478 - 484

Published: May 4, 2023

Although all multicellular organisms have germ line-encoded innate receptors to sense pathogen-associated molecular patterns, vertebrates also evolved adaptive immunity based on somatically generated antigen B and T cells. Because randomly may react with self-antigens, tolerance checkpoints operate limit but not completely prevent autoimmunity. These two systems are intricately linked, playing an instrumental role in the induction of antiviral immunity. In this work, we review how inborn errors can instigate cell Increased nucleic acid sensing, often resulting from defects metabolizing pathways or retroelement control, break converge into TLR7-, cGAS-STING-, MAVS-dominant signaling pathways. The syndromes span a spectrum that ranges chilblain systemic lupus severe interferonopathies.

Language: Английский

Citations

27
SLC15A4 controls endolysosomal TLR7–9 responses by recruiting the innate immune adaptor TASL DOI Creative Commons
Haobo Zhang, Léa Bernaleau, Maeva Delacrétaz

et al.

Cell Reports, Journal Year: 2023, Volume and Issue: 42(8), P. 112916 - 112916

Published: July 31, 2023

Endolysosomal Toll-like receptors (TLRs) play crucial roles in immune responses to pathogens, while aberrant activation of these pathways is associated with autoimmune diseases, including systemic lupus erythematosus (SLE). The endolysosomal solute carrier family 15 member 4 (SLC15A4) required for TLR7/8/9-induced and disease development SLE models. SLC15A4 has been proposed affect TLR7-9 through its transport activity, as well by assembling an IRF5-activating complex TASL, but the relative contribution functions remains unclear. Here, we show that essential role recruit TASL endolysosomes, activity dispensable when tethered this compartment. Endolysosomal-localized rescues TLR7-9-induced IRF5 interferon β cytokine production SLC15A4-deficient cells. acts signaling scaffold, function control TLR7-9-mediated inflammatory responses. These findings support targeting SLC15A4-TASL a potential therapeutic strategy related diseases.

Language: Английский

Citations

26
Revisiting p38 Mitogen-Activated Protein Kinases (MAPK) in Inflammatory Arthritis: A Narrative of the Emergence of MAPK-Activated Protein Kinase Inhibitors (MK2i) DOI Creative Commons
Payal Ganguly, Tom Macleod, Chi Huey Wong

et al.

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(9), P. 1286 - 1286

Published: Sept. 12, 2023

The p38 mitogen-activated protein kinase (p38-MAPK) is a crucial signaling pathway closely involved in several physiological and cellular functions, including cell cycle, apoptosis, gene expression, responses to stress stimuli. It also plays central role inflammation immunity. Owing disparate p38-MAPK it has thus far formed an elusive drug target with failed clinical trials inflammatory diseases due challenges hepatotoxicity, cardiac toxicity, lack of efficacy, tachyphylaxis, which brief initial improvement rapid disease rebound. To overcome these limitations, downstream antagonism the MAPK-activated (MAPKAPK, known as MK2) blockade demonstrated potential abrogate without prior recognized toxicities. Such MK2 inhibition (MK2i) associated robust suppression key pro-inflammatory cytokines, TNFα IL-6 others experimental systems vitro. Considering this recent evidence regarding MK2i arthritis, we revisit discuss literature encompassing inhibitors focus on pathway. We then highlight how novel strategies, although encouraging pre-clinical arena, may either show for efficacy or emergent human data from different settings.

Language: Английский

Citations

26
Genkwanin: An emerging natural compound with multifaceted pharmacological effects DOI Creative Commons
Naoual El Menyiy, Sara Aboulaghras, Saad Bakrim

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 165, P. 115159 - 115159

Published: July 21, 2023

Plant bioactive molecules could play key preventive and therapeutic roles in chronological aging the pathogenesis of many chronic diseases, often accompanied by increased oxidative stress low-grade inflammation. Dietary antioxidants, including genkwanin, decrease expression pro-inflammatory cytokines or pathways. The present study is first comprehensive review a methoxyflavone found several plant species. Indeed, natural sources, pharmacokinetics biological properties were discussed highlighted detail. This analyzed considered all original studies related to identification, isolation, quantification, investigation pharmacological genkwanin. We consulted published papers peer-reviewed journals English language from inception each database 12 May 2023. Different phytochemical demonstrated that genkwanin non-glycosylated flavone isolated medicinal plants such as Genkwa Flos, Rosmarinus officinalis, Salvia Leonurus sibiricus. In vitro vivo investigations showed Genkwanin exhibits remarkable antioxidant anti-inflammatory activities, via activation glucokinase, has shown antihyperglycemic activity with potential role against metabolic syndrome diabetes. Additionally, it revealed cardioprotective neuroprotective properties, thus reducing risk cardiovascular diseases assisting neurodegenerative diseases. Furthermore, other like antitumor capability, antibacterial, antiviral, dermato-protective effects. involved mechanisms include sub-cellular, cellular molecular actions at different levels inducing apoptosis inhibiting growth proliferation cancer cells. Despite findings preclinical have effects its diverse action, additional research required comprehensively explore potential. Primarily, extensive should be carried out enhance our understanding molecule's pharmacodynamic pharmacokinetic Moreover, toxicological clinical undertaken assess safety efficacy These forthcoming are utmost importance fully unlocking this molecule realm applications.

Language: Английский

Citations

25