JAK-STAT signaling maintains homeostasis in T cells and macrophages DOI Creative Commons
Nikolaus Fortelny, Matthias Farlik, Victoria Fife-Gernedl

et al.

Nature Immunology, Journal Year: 2024, Volume and Issue: 25(5), P. 847 - 859

Published: April 24, 2024

Abstract Immune cells need to sustain a state of constant alertness over lifetime. Yet, little is known about the regulatory processes that control fluent and fragile balance called homeostasis. Here we demonstrate JAK-STAT signaling, beyond its role in immune responses, major regulator cell We investigated JAK-STAT-mediated transcription chromatin accessibility across 12 mouse models, including knockouts all STAT factors TYK2 kinase. Baseline signaling was detected CD8 + T macrophages unperturbed mice—but abrogated unstimulated deprived their normal tissue context. observed diverse gene-regulatory programs, effects STAT2 IRF9 were independent STAT1. In summary, our large-scale dataset integrative analysis mutant wild-type mice uncovered crucial cells, where it contributes poised epigenetic transcriptional helps prepare these for rapid response stimuli.

Language: Английский

Role of the cGAS–STING pathway in systemic and organ-specific diseases DOI Open Access
Sladjana Skopelja‐Gardner, Jie An, Keith B. Elkon

et al.

Nature Reviews Nephrology, Journal Year: 2022, Volume and Issue: 18(9), P. 558 - 572

Published: June 22, 2022

Language: Английский

Citations

170
Autoinflammation and autoimmunity across rheumatic and musculoskeletal diseases DOI
Zoltán Szekanecz, Iain B. McInnes, Georg Schett

et al.

Nature Reviews Rheumatology, Journal Year: 2021, Volume and Issue: 17(10), P. 585 - 595

Published: Aug. 2, 2021

Language: Английский

Citations

169
Identification of key biomarkers and immune infiltration in systemic lupus erythematosus by integrated bioinformatics analysis DOI Creative Commons
Xingwang Zhao, Longlong Zhang, Juan Wang

et al.

Journal of Translational Medicine, Journal Year: 2021, Volume and Issue: 19(1)

Published: Jan. 19, 2021

Abstract Background Systemic lupus erythematosus (SLE) is a multisystemic, chronic inflammatory disease characterized by destructive systemic organ involvement, which could cause the decreased functional capacity, increased morbidity and mortality. Previous studies show that SLE autoimmune, processes, tissue destruction. Some seriously-ill patients develop into nephritis. However, underlying molecular events of needs to be further resolved. Methods The expression profiles GSE144390, GSE4588, GSE50772 GSE81622 were downloaded from Gene Expression Omnibus (GEO) database obtain differentially expressed genes (DEGs) between healthy samples. gene ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) pathway enrichments DEGs performed metascape etc. online analyses. protein–protein interaction (PPI) networks constructed GENEMANIA software. We Set Enrichment Analysis (GSEA) understand functions hub gene, Weighted co‐expression network analysis (WGCNA) would utilized build network, most significant module was identified. CIBERSORT tools have facilitated immune cell infiltration patterns diseases. receiver operating characteristic (ROC) analyses conducted explore value for diagnosis. Results In total, 6 (IFI27, IFI44, IFI44L, IFI6, EPSTI1 OAS1) screened, Biological identified key related pathways, modules in SLE. IFI27 may closely correlated with occurrence found an moncytes, while NK cells resting infiltrated less Conclusion pathogenesis SLE, represents new candidate marker progression Moreover plays important role progession

Language: Английский

Citations

144
B-cell depleting therapies may affect susceptibility to acute respiratory illness among patients with multiple sclerosis during the early COVID-19 epidemic in Iran DOI Creative Commons
Farinaz Safavi, Bardia Nourbakhsh,

Amir Reza Azimi

et al.

Multiple Sclerosis and Related Disorders, Journal Year: 2020, Volume and Issue: 43, P. 102195 - 102195

Published: May 13, 2020

ObjectiveTo determine whether the course of COVID-19 is more severe in patients with MS and if disease-modifying treatments (DMTs) affect risk contracting disease.MethodsIn a cross-sectional survey, data were collected by sending questionnaire to 2000 demyelinating disease through an online portal system. Collected included current DMT patient-reported disability level, history recent sick contact, fever, respiratory symptoms, diagnosis COVID-19, disposition after diagnosis. We defined COVID-19-suspect group as having fever cough or shortness breath, presumptive based on suggestive chest computed tomography. calculated proportion compared their demographics, clinical characteristics, categories rest survey-responders, using univariable multivariable models.ResultsOut 712 patients, 34 (4.8%) fulfilled our criteria for being group. Only two required hospitalization. No patient intensive care. In model, duration (p-value=0.017), category (p-value=0.030), contact (p-values<0.001) associated Being B-cell depleting antibodies (as non-cell depleting, trafficking inhibitor DMTs) was 2.6-fold increase (RR: 3.55, 95%CI: 1.45, 8.68, p-value=0.005).ConclusionsThe infection suspected mild moderate, all had full recovery. may susceptibility COVID-19.

Language: Английский

Citations

143
Discrimination and systemic inflammation: A critical review and synthesis DOI
Adolfo G. Cuevas, Anthony D. Ong, Keri Carvalho

et al.

Brain Behavior and Immunity, Journal Year: 2020, Volume and Issue: 89, P. 465 - 479

Published: July 17, 2020

Language: Английский

Citations

138
Large-scale and high-resolution mass spectrometry-based proteomics profiling defines molecular subtypes of esophageal cancer for therapeutic targeting DOI Creative Commons
Wei Liu, Lei Xie, Yaohui He

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Aug. 16, 2021

Abstract Esophageal cancer (EC) is a type of aggressive without clinically relevant molecular subtypes, hindering the development effective strategies for treatment. To define subtypes EC, we perform mass spectrometry-based proteomic and phosphoproteomics profiling EC tumors adjacent non-tumor tissues, revealing catalog proteins phosphosites that are dysregulated in ECs. The cohort stratified into two subtypes—S1 S2—based on analysis, with S2 subtype characterized by upregulation spliceosomal ribosomal proteins, being more aggressive. Moreover, identify signature composed ELOA SCAF4, construct diagnostic prognostic model. Potential drugs predicted treating patients subtype, three candidate validated to inhibit EC. Taken together, our analysis thus providing potential therapeutic outlook improving disease outcomes

Language: Английский

Citations

124
Emerging concepts of type I interferons in SLE pathogenesis and therapy DOI
Antonios Psarras, Miriam Wittmann, Edward M Vital

et al.

Nature Reviews Rheumatology, Journal Year: 2022, Volume and Issue: unknown

Published: Sept. 12, 2022

Language: Английский

Citations

90
Pathogenesis and treatment of Sjogren’s syndrome: Review and update DOI Creative Commons
Qipeng Zhan, Jianan Zhang, Yubin Lin

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 2, 2023

Sjogren’s syndrome (SS) is a chronic autoimmune disease accompanied by multiple lesions. The main manifestations include dryness of the mouth and eyes, along with systemic complications (e.g., pulmonary disease, kidney injury, lymphoma). In this review, we highlight that IFNs, Th17 cell-related cytokines (IL-17 IL-23), B (TNF BAFF) are crucial for pathogenesis SS. We also summarize advances in experimental treatment strategies, including targeting Treg/Th17, mesenchymal stem cell treatment, BAFF, inhibiting JAK pathway, et al. Similar to SLE, RA, MS, biotherapeutic strategies SS consist neutralizing antibodies inflammation-related receptor blockers proinflammatory signaling pathways. However, clinical research on therapy comparatively rare. Moreover, differences curative effects immunotherapies among other diseases not fully understood. emphasize targeted drugs, low-side-effect combination therapies should be focus future research.

Language: Английский

Citations

87
An adjuvant strategy enabled by modulation of the physical properties of microbial ligands expands antigen immunogenicity DOI Creative Commons
Francesco Borriello, Valentina Poli, Ellen Shrock

et al.

Cell, Journal Year: 2022, Volume and Issue: 185(4), P. 614 - 629.e21

Published: Feb. 1, 2022

Language: Английский

Citations

81
Type I IFNs promote cancer cell stemness by triggering the epigenetic regulator KDM1B DOI Creative Commons
Martina Musella, Andrea Guarracino,

Nicoletta Manduca

et al.

Nature Immunology, Journal Year: 2022, Volume and Issue: 23(9), P. 1379 - 1392

Published: Aug. 24, 2022

Cancer stem cells (CSCs) are a subpopulation of cancer endowed with high tumorigenic, chemoresistant and metastatic potential. Nongenetic mechanisms acquired resistance increasingly being discovered, but molecular insights into the evolutionary process CSCs limited. Here, we show that type I interferons (IFNs-I) function as hubs during immunogenic chemotherapy, triggering epigenetic regulator demethylase 1B (KDM1B) to promote an adaptive, yet reversible, transcriptional rewiring towards stemness immune escape. Accordingly, KDM1B inhibition prevents appearance IFN-I-induced CSCs, both in vitro vivo. Notably, heterogeneous terms multidrug resistance, plasticity, invasiveness immunogenicity. Moreover, breast (BC) patients receiving anthracycline-based positively correlated CSC signatures. Our study identifies IFN-I → axis potent engine cell reprogramming, supporting targeting attractive adjunctive drugs prevent expansion increase long-term benefit therapy.

Language: Английский

Citations

78