BCL3, GBP1, IFI16, and CCR1 as potential brain-derived biomarkers for parietal grey matter lesions in multiple sclerosis DOI Creative Commons
Hua Guo, Zhaoqing Li, Yanqing Wang

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Nov. 18, 2024

Multiple Sclerosis (MS) is a chronic autoimmune disease of the central nervous system, progressing from Relapsing–Remitting MS (RRMS) to Secondary Progressive (SPMS) in many cases. The transition involves complex biological changes. Our study aims identify potential biomarkers for distinguishing SPMS by analyzing gene expression differences between normal-appearing and lesioned parietal grey matter, which may also contribute understand pathogenesis SPMS. We utilized public datasets Gene Expression Omnibus (GEO), applying bioinformatics machine learning techniques including Weighted Co-expression Network Analysis (WGCNA), Kyoto Encyclopedia Genes Genomes (KEGG), Ontology (GO) enrichment analysis, protein–protein interaction (PPI) networks, Least Absolute Shrinkage Selection Operator (LASSO), Random Forest (RF) predictive model construction. included analyses immune cell infiltration. identified 359 DEGs, with 105 up-regulated 254 down-regulated. WGCNA 264 common genes, were subjected KEGG GO analyses, highlighting their role response viral infection pathways. Four genes (BCL3, GBP1, IFI16, CCR1) as key SPMS, supported LASSO regression RF analyses. These further validated through receiver operating characteristic (ROC) curves, demonstrating significant provides novel set matter cases, offering diagnosis targeted therapeutic strategies. link closely pathology, especially regarding system modulation.

Language: Английский

Interferon- γ and infectious diseases: Lessons and prospects DOI
Jean‐Laurent Casanova, John D. MacMicking, Carl Nathan

et al.

Science, Journal Year: 2024, Volume and Issue: 384(6693)

Published: April 18, 2024

Infectious diseases continue to claim many lives. Prevention of morbidity and mortality from these would benefit not just new medicines vaccines but also a better understanding what constitutes protective immunity. Among the major immune signals that mobilize host defense against infection is interferon-γ (IFN-γ), protein secreted by lymphocytes. Forty years ago, IFN-γ was identified as macrophage-activating factor, and, in recent years, there has been resurgent interest biology its role human defense. Here we assess current IFN-γ, revisit designation an "interferon," weigh prospects therapeutic globally pervasive microbial pathogens.

Language: Английский

Citations

56
Molecular definition of the endogenous Toll-like receptor signalling pathways DOI
Daniel Fisch, Tian Zhang,

He Sun

et al.

Nature, Journal Year: 2024, Volume and Issue: 631(8021), P. 635 - 644

Published: July 3, 2024

Language: Английский

Citations

25
Inducible antibacterial responses in macrophages DOI
Matthew J. Sweet, Divya Ramnath, Amit Singhal

et al.

Nature reviews. Immunology, Journal Year: 2024, Volume and Issue: 25(2), P. 92 - 107

Published: Sept. 18, 2024

Language: Английский

Citations

21
Phagosome-mediated anti-bacterial immunity is governed by the proton-activated chloride channel in peritoneal macrophages DOI Creative Commons
Yi Cheng, Jiachen Chu, Nathachit Limjunyawong

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 2, 2025

Phagosome degradation is an evolutionally conserved and highly effective innate immune response against pathogen infections. The success of this process relies on the ability phagocytes to regulate maturation phagosomes. However, underlying molecular mechanisms its roles in shaping downstream activation remain poorly understood. Here, we identify proton-activated chloride (PAC) channel as a key negative regulator phagosome maturation. PAC deletion enhanced phagosomal acidification protease activities, leading augmented bacterial killing large peritoneal macrophages (LPMs) upon Escherichia coli infection mice. Surprisingly, also stimulated STING-IRF3-interferon responses inflammasome LPMs, both which are deletion. increased pyroptosis induced unexpected release cleaved gasdermin D, localized surface bacteria peritoneum further contributed their killing. Finally, clearance by PAC-deficient LPMs reduced proinflammatory cell infiltration overall inflammation, resulting improved survival Our study thus provides new insights into mechanism dynamics host defense following phagosome-mediated macrophages. It highlights potential targeting therapeutic strategy for treating mediates during promotes interferon signaling inflammasome-mediated D secretion

Language: Английский

Citations

1
Exploring the shared gene signatures and mechanism among three autoimmune diseases by bulk RNA sequencing integrated with single-cell RNA sequencing analysis DOI Creative Commons
Xiao-Fang Liu, Bin Li, Yuxi Lin

et al.

Frontiers in Molecular Biosciences, Journal Year: 2025, Volume and Issue: 11

Published: Jan. 7, 2025

Emerging evidence underscores the comorbidity mechanisms among autoimmune diseases (AIDs), with innovative technologies such as single-cell RNA sequencing (scRNA-seq) significantly advancing explorations in this field. This study aimed to investigate shared genes three AIDs-Multiple Sclerosis (MS), Systemic Lupus Erythematosus (SLE), and Rheumatoid Arthritis (RA) using bioinformatics databases, identify potential biomarkers for early diagnosis. We retrieved transcriptomic data of MS, SLE, RA patients from public databases. Weighted Gene Co-Expression Network Analysis (WGCNA) was employed construct gene co-expression networks disease-associated modules. Functional enrichment analyses Protein-Protein Interaction (PPI) network constructed. used machine learning algorithms select candidate evaluate their diagnostic value. The Cibersort algorithm scRNA-seq analysis performed key expression patterns assess infiltration immune cells MS patients. Finally, biomarkers' validated human mice experiments. Several were identified, which play crucial roles responses inflammation regulation. PPI highlighted hub genes, some selected through algorithms. Receiver Operating Characteristic (ROC) curve indicated that had high value (Area Under Curve, AUC >0.7). Immune cell pattern showed significant differences various revealed clusters upregulated single cerebrospinal fluid EAE mose model. Validation clinical samples confirmed biomarkers. identified proposed These are pivotal regulating responses, providing new targets theoretical basis diagnosis treatment diseases.

Language: Английский

Citations

0
Transcriptome-proteome integration analysis identifies elevated expression of LARP7 promoting the tumorigenesis and development of gastrointestinal stromal tumors DOI Creative Commons
Heng Zheng, Yong Pan

Translational Oncology, Journal Year: 2025, Volume and Issue: 53, P. 102316 - 102316

Published: Feb. 10, 2025

Language: Английский

Citations

0
Targeting PIM1 by Bruceine D attenuates skin fibrosis via myofibroblast ferroptosis DOI Creative Commons
Jianzhang Wang,

Yajuan Song,

Xiao-Ying Tan

et al.

Redox Biology, Journal Year: 2025, Volume and Issue: unknown, P. 103619 - 103619

Published: March 1, 2025

Language: Английский

Citations

0
Brucella infection induces chromatin restructuring in host cells to activate immune responses DOI Creative Commons
Dejian Xie, Hu Xu,

Changwei Su

et al.

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

Published: June 5, 2025

Background Brucella spp., facultative intracellular pathogens that cause brucellosis, drive pathogenesis by invading host cells and establishing persistence. While their molecular mechanisms are well-characterized, how induces chromatin restructuring in remains poorly understood, representing a critical gap host-pathogen interaction research. Methods Using an established vitro infection model of -infected RAW264.7 murine macrophages, we integrated Hi-C, ATAC-seq, RNA-seq to generate multi-omics datasets. Multidimensional comparative genomics approaches were employed systematically map infection-induced changes architecture functional genomic organization. Results Our findings unveiled substantial alterations the architecture, characterized reduction B-B compartment regions interactions, increase A-B diminished long-range contacts. Crucially, reshaped compartmentalization, activating interferon-stimulated genes (ISGs) transitioning from B A. Enhanced sub-TADs interactions within ISG clusters further facilitated coordinated expression. Additionally, remodeled loop structures, strengthening linked immune-related gene activation. Conclusion These results demonstrate undergo remodeling during acute as defense mechanism against pathogen invasion. provide insights into suggest potential epigenetic targets for managing brucellosis.

Language: Английский

Citations

0
IFNs in host defence and parasite immune evasion during Toxoplasma gondii infections DOI Creative Commons

Carsten G. K. Lüder

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 7, 2024

Interferons (IFNs) are a family of cytokines with diverse functions in host resistance to pathogens and immune regulation. Type II IFN, i.e. IFN-γ, is widely recognized as major mediator intracellular pathogens, including the protozoan Toxoplasma gondii . More recently, IFN-α/β, type I IFNs, IFN-λ (type III IFN) have been identified also play important roles during T. infections. This parasite widespread pathogen humans animals, it model organism study cell-mediated responses infection. Its success depends, among other factors, on ability counteract IFN system, both at level IFN-mediated gene expression IFN-regulated effector molecules. Here, review recent advances our understanding molecular mechanisms underlying regulation discuss those that has evolved efficiently evade immunity. Knowledge these fascinating host-parasite interactions their signalling machineries crucial for deeper pathogenesis toxoplasmosis, might identify potential targets parasite-directed or host-directed supportive therapies combat more effectively.

Language: Английский

Citations

3
GBP1 promotes acute rejection after liver transplantation by inducing Kupffer cells pyroptosis DOI Creative Commons

Haojiang Duan,

Qingyao Chang,

Huaxing Ding

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2024, Volume and Issue: 1871(3), P. 167644 - 167644

Published: Dec. 27, 2024

Language: Английский

Citations

3