keyword
https://read.qxmd.com/read/38510251/functional-significance-of-dna-methylation-epigenetic-insights-into-sj%C3%A3-gren-s-syndrome
#21
REVIEW
Yanqing Wang, Farooq Riaz, Wei Wang, Jincheng Pu, Yuanyuan Liang, Zhenzhen Wu, Shengnan Pan, Jiamin Song, Lufei Yang, Youwei Zhang, Huihong Wu, Fang Han, Jianping Tang, Xuan Wang
Sjögren's syndrome (SjS) is a systemic, highly diverse, and chronic autoimmune disease with a significant global prevalence. It is a complex condition that requires careful management and monitoring. Recent research indicates that epigenetic mechanisms contribute to the pathophysiology of SjS by modulating gene expression and genome stability. DNA methylation, a form of epigenetic modification, is the fundamental mechanism that modifies the expression of various genes by modifying the transcriptional availability of regulatory regions within the genome...
2024: Frontiers in Immunology
https://read.qxmd.com/read/38508295/type-i-interferon-associated-epistasis-may-contribute-to-early-disease-onset-and-high-disease-activity-in-juvenile-onset-lupus
#22
REVIEW
Yves Renaudineau, Amandine Charras, Valentina Natoli, Mathieu Fusaro, Eve M D Smith, Michael W Beresford, Christian M Hedrich
Pathologic type I interferon (T1IFN) expression is a key feature in systemic lupus erythematosus (SLE) that associates with disease activity. When compared to adult-onset disease, juvenile-onset (j)SLE is characterized by increased disease activity and damage, which likely relates to increased genetic burden. To identify T1IFN-associated gene polymorphisms (TLR7, IRAK1, miR-3142/miR-146a, IRF5, IRF7, IFIH1, IRF8, TYK2, STAT4), identify long-range linkage disequilibrium and gene:gene interrelations, 319 jSLE patients were genotyped using panel sequencing...
March 18, 2024: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://read.qxmd.com/read/38506049/combining-vps34-inhibitors-with-sting-agonists-enhances-type-i-interferon-signaling-and-anti-tumor-efficacy
#23
JOURNAL ARTICLE
Yasmin Yu, Madhumita Bogdan, Muhammad Zaeem Noman, Santiago Parpal, Elisabetta Bartolini, Kris Van Moer, Simone Caroline Kleinendorst, Kristine Bilgrav Saether, Lionel Trésaugues, Camilla Silvander, Johan Lindström, Jodi Simeon, Mary Jane Timson, Hikmat Al-Hashimi, Bryan D Smith, Daniel L Flynn, Andrey Alexeyenko, Jenny Viklund, Martin Andersson, Jessica Martinsson, Katja Pokrovskaja Tamm, Angelo De Milito, Bassam Janji
An immunosuppressive tumor microenvironment promotes tumor growth and is one of the main factors limiting the response to cancer immunotherapy. We have previously reported that inhibition of vacuolar protein sorting 34 (VPS34), a crucial lipid kinase in the autophagy/endosomal trafficking pathway, decreases tumor growth in several cancer models, increases infiltration of immune cells and sensitizes tumors to anti-programmed cell death protein 1/programmed cell death 1 ligand 1 therapy by upregulation of C-C motif chemokine 5 (CCL5) and C-X-C motif chemokine 10 (CXCL10) chemokines...
March 20, 2024: Molecular Oncology
https://read.qxmd.com/read/38504978/inhibitory-receptors-of-plasmacytoid-dendritic-cells-as-possible-targets-for-checkpoint-blockade-in-cancer
#24
REVIEW
Laura Tiberio, Mattia Laffranchi, Giovanni Zucchi, Valentina Salvi, Tiziana Schioppa, Silvano Sozzani, Annalisa Del Prete, Daniela Bosisio
Plasmacytoid dendritic cells (pDCs) are the major producers of type I interferons (IFNs), which are essential to mount antiviral and antitumoral immune responses. To avoid exaggerated levels of type I IFNs, which pave the way to immune dysregulation and autoimmunity, pDC activation is strictly regulated by a variety of inhibitory receptors (IRs). In tumors, pDCs display an exhausted phenotype and correlate with an unfavorable prognosis, which largely depends on the accumulation of immunosuppressive cytokines and oncometabolites...
2024: Frontiers in Immunology
https://read.qxmd.com/read/38502642/establishment-of-a-lethal-mouse-model-of-emerging-tick-borne-orthonairovirus-infections
#25
JOURNAL ARTICLE
Takuma Ariizumi, Koshiro Tabata, Yukari Itakura, Hiroko Kobayashi, William W Hall, Michihito Sasaki, Hirofumi Sawa, Keita Matsuno, Yasuko Orba
Emerging and reemerging tick-borne orthonairovirus infections (family Nairoviridae), which are genetically distinct from Crimean-Congo hemorrhagic fever virus, have been recently reported in East Asia. Here, we have established a mouse infection model using type-I/II interferon receptor-knockout mice (AG129) both for a better understanding the pathogenesis of these infections and validation of antiviral agents using Yezo virus (YEZV), a novel virus causing febrile illnesses associated with tick bites in Japan and China...
March 19, 2024: PLoS Pathogens
https://read.qxmd.com/read/38500667/influence-of-intestinal-microbial-metabolites-on-the-abscopal-effect-after-radiation-therapy-combined-with-immune-checkpoint-inhibitors
#26
JOURNAL ARTICLE
Hannah Felchle, Julia Gissibl, Laura Lansink Rotgerink, Sophie M Nefzger, Caroline N Walther, Vincent R Timnik, Stephanie E Combs, Julius C Fischer
BACKGROUND: Most clinical studies failed to elicit a strong antitumor immune response and subsequent systemic tumor regression after radiation therapy (RT), even in combination with the immune checkpoint inhibitors (ICI) anti-CTLA4 or anti-PD1. Mechanistically, type I interferon (IFN-I) activation is essential for the development of such abscopal effects (AE); however, mechanisms driving or limiting IFN-I activation are ill defined. Groundbreaking discoveries have shown that antibiotics (ABx) can affect oncological outcomes and that microbiota-derived metabolites can modulate systemic antitumor immunity...
May 2024: Clinical and Translational Radiation Oncology
https://read.qxmd.com/read/38499217/construction-and-analysis-of-the-immune-effect-of-two-different-vaccine-types-based-on-vibrio-harveyi-vgrg
#27
JOURNAL ARTICLE
Xiangyu Du, Minjie Kang, Chunhuan Yang, Xinping Yao, Lvliang Zheng, Ying Wu, Panpan Zhang, Han Zhang, Yongcan Zhou, Yun Sun
Vibrio harveyi poses a significant threat to fish and invertebrates in mariculture, resulting in substantial financial repercussions for the aquaculture sector. Valine-glycine repeat protein G (VgrG) is essential for the type VI secretion system's (T6SS) assembly and secretion. VgrG from V. harveyi QT520 was cloned and analyzed in this study. The localization of VgrG was determined by Western blot, which revealed that it was located in the cytoplasm, secreted extracellularly, and attached to the membrane. The effectiveness of two vaccinations against V...
March 16, 2024: Fish & Shellfish Immunology
https://read.qxmd.com/read/38496444/myc-dysregulation-in-activated-macrophages-initiates-iron-mediated-lipid-peroxidation-that-fuels-type-i-interferon-and-compromises-tb-resistance
#28
Shivraj M Yabaji, Vadim Zhernovkov, Prasanna Babu Araveti, Suruchi Lata, Oleksii S Rukhlenko, Salam Al Abdullatif, Yuriy Alekseev, Qicheng Ma, Gargi Dayama, Nelson C Lau, William R Bishai, Nicholas A Crossland, Joshua D Campbell, Boris N Kholodenko, Alexander A Gimelbrant, Lester Kobzik, Igor Kramnik
A quarter of human population is infected with Mycobacterium tuberculosis , but less than 10% of those infected develop clinical, mostly pulmonary, TB. To dissect mechanisms of susceptibility in immunocompetent individuals, we developed a genetically defined sst1 -susceptible mouse model that uniquely reproduces a defining feature of human TB: development of necrotic lung lesions after infection with virulent Mtb. In this study, we explored the connectivity of the sst1 -regulated pathways during prolonged macrophage activation with TNF...
March 10, 2024: bioRxiv
https://read.qxmd.com/read/38495892/interferon-lambda-in-respiratory-viral-infection-immunomodulatory-functions-and-antiviral-effects-in-epithelium
#29
REVIEW
Yong-Guang Liu, Su-Wei Jin, Shan-Shan Zhang, Tian-Ji Xia, Yong-Hong Liao, Rui-Le Pan, Ming-Zhu Yan, Qi Chang
Type III interferon (IFN-λ), a new member of the IFN family, was initially considered to possess antiviral functions similar to those of type I interferon, both of which are induced via the JAK/STAT pathway. Nevertheless, recent findings demonstrated that IFN-λ exerts a nonredundant antiviral function at the mucosal surface, preferentially produced in epithelial cells in contrast to type I interferon, and its function cannot be replaced by type I interferon. This review summarizes recent studies showing that IFN-λ inhibits the spread of viruses from the cell surface to the body...
2024: Frontiers in Immunology
https://read.qxmd.com/read/38495890/trim28-facilitates-type-i-interferon-activation-by-targeting-tbk1
#30
JOURNAL ARTICLE
Fang Hua, Tim Nass, Kislay Parvatiyar
Type I interferons play a fundamental role in innate host defense against viral infections by eliciting the induction of an antiviral gene program that serves to inhibit viral replication. Activation of type I interferon is regulated by the IRF3 transcription factor, which undergoes phosphorylation-dependent activation by the upstream kinase, TBK1, during viral infection. However, the mechanisms by which TBK1 achieves activation to support signaling to IRF3 remain incompletely understood. Here we identified the E3 ubiquitin ligase, tripartite motif containing 28 (TRIM28), as a positive regulator of type I interferon activation by facilitating TBK1 signaling...
2024: Frontiers in Immunology
https://read.qxmd.com/read/38495845/modifying-mirs-for-effective-reprogramming-of-fibroblasts-to-cardiomyocytes
#31
JOURNAL ARTICLE
Xinghua Wang, Syeda S Baksh, Richard E Pratt, Victor J Dzau, Conrad P Hodgkinson
Reprogramming scar fibroblasts into cardiomyocytes has been proposed to reverse the damage associated with myocardial infarction. However, the limited improvement in cardiac function calls for enhanced strategies. We reported enhanced efficacy of our miR reprogramming cocktail miR combo (miR-1, miR-133a, miR-208a, and miR-499) via RNA-sensing receptor stimulation. We hypothesized that we could combine RNA-sensing receptor activation with fibroblast reprogramming by chemically modifying miR combo. To test the hypothesis, miR combo was modified to enhance interaction with the RNA-sensing receptor Rig1 via the addition of a 5'-triphosphate (5'ppp) group...
June 11, 2024: Molecular Therapy. Nucleic Acids
https://read.qxmd.com/read/38494904/lung-gene-expression-suggests-roles-for-interferon-stimulated-genes-and-adenosine-deaminase-acting-against-rna-1-in-pathologic-responses-to-diisocyanate
#32
JOURNAL ARTICLE
Adam V Wisnewski, Jian Liu
Mechanisms underlying methylene diphenyl diisocyanate (MDI) and other low molecular weight chemical-induced asthma are unclear and appear distinct from those of high molecular weight (HMW) allergen-induced asthma. We sought to elucidate molecular pathways that differentiate asthma-like pathogenic vs nonpathogenic responses to respiratory tract MDI exposure in a murine model. Lung gene expression differences in MDI exposed immune-sensitized and nonsensitized mice vs unexposed controls were measured by microarrays, and associated molecular pathways were identified through bioinformatic analyses and further compared with published studies of a prototypic HMW asthmagen (ovalbumin)...
March 18, 2024: Chemical Research in Toxicology
https://read.qxmd.com/read/38492861/sting-activating-cyclic-dinucleotide-manganese-nanoparticles-evoke-robust-immunity-against-acute-myeloid-leukemia
#33
JOURNAL ARTICLE
Marisa E Aikins, Xiaoqi Sun, Hannah Dobson, Xingwu Zhou, Yao Xu, Yu Leo Lei, James J Moon
Acute myeloid leukemia (AML) is one of the most common types of leukemia in adults with a 5-year survival rate of 30.5%. These poor patient outcomes are attributed to tumor relapse, stemming from ineffective innate immune activation, T cell tolerance, and a lack of immunological memory. Thus, new strategies are needed to activate innate and effector immune cells and evoke long-term immunity against AML. One approach to address these issues is through Stimulator of Interferon Genes (STING) pathway activation, which produces Type I Interferons (Type I IFN) critical for innate and adaptive immune activation...
March 20, 2024: Journal of Controlled Release
https://read.qxmd.com/read/38489371/increased-genomic-instability-and-reshaping-of-tissue-microenvironment-underlie-oncogenic-properties-of-arid1a-mutations
#34
JOURNAL ARTICLE
Alessandro D'Ambrosio, Davide Bressan, Elisa Ferracci, Francesco Carbone, Patrizia Mulè, Federico Rossi, Caterina Barbieri, Elisa Sorrenti, Gaia Fiaccadori, Thomas Detone, Elena Vezzoli, Salvatore Bianchi, Chiara Sartori, Simona Corso, Akihisa Fukuda, Giovanni Bertalot, Andrea Falqui, Mattia Barbareschi, Alessandro Romanel, Diego Pasini, Fulvio Chiacchiera
Oncogenic mutations accumulating in many chromatin-associated proteins have been identified in different tumor types. With a mutation rate from 10 to 57%, ARID1A has been widely considered a tumor suppressor gene. However, whether this role is mainly due to its transcriptional-related activities or its ability to preserve genome integrity is still a matter of intense debate. Here, we show that ARID1A is largely dispensable for preserving enhancer-dependent transcriptional regulation, being ARID1B sufficient and required to compensate for ARID1A loss...
March 15, 2024: Science Advances
https://read.qxmd.com/read/38487540/the-ifih1-a946t-risk-variant-promotes-diabetes-in-a-sex-dependent-manner
#35
JOURNAL ARTICLE
Amanda J Stock, Pierina Gonzalez Paredes, Luciana Previato de Almeida, Stanley D Kosanke, Srinivaas Chetlur, Hannah Budde, Paul Wakenight, Theresa A Zwingman, Aaron B I Rosen, Eric J Allenspach, Kathleen J Millen, Jane H Buckner, David J Rawlings, Jacquelyn A Gorman
Type 1 diabetes (T1D) is an autoimmune disease in which pancreatic islet β-cells are attacked by the immune system, resulting in insulin deficiency and hyperglycemia. One of the top non-synonymous single-nucleotide polymorphisms (SNP) associated with T1D is in the interferon-induced helicase C domain-containing protein 1 ( IFIH1 ), which encodes an anti-viral cytosolic RNA sensor. This SNP results in an alanine to threonine substitution at amino acid 946 ( IFIH1A946T ) and confers an increased risk for several autoimmune diseases, including T1D...
2024: Frontiers in Immunology
https://read.qxmd.com/read/38483900/housekeeping-u1-snrna-facilitates-antiviral-innate-immunity-by-promoting-trim25-mediated-rig-i-activation
#36
JOURNAL ARTICLE
Fan Zhang, Siying Liu, Zigang Qiao, Liang Li, Yu Han, Jiya Sun, Chenglong Ge, Jingfei Zhu, Dapei Li, Haiping Yao, Huiying Zhang, Jianfeng Dai, Yongdong Yan, Zhengrong Chen, Lichen Yin, Feng Ma
U1 small nuclear RNA (snRNA) is an abundant and evolutionarily conserved 164-nucleotide RNA species that functions in pre-mRNA splicing, and it is considered to be a housekeeping non-coding RNA. However, the role of U1 snRNA in regulating host antiviral immunity remains largely unexplored. Here, we find that RNVU1-18, a U1 pseudogene, is significantly upregulated in the host infected with RNA viruses, including influenza and respiratory syncytial virus. Overexpression of U1 snRNA protects cells against RNA viruses, while knockdown of U1 snRNA leads to more viral burden in vitro and in vivo...
March 13, 2024: Cell Reports
https://read.qxmd.com/read/38483060/siah1-modulates-antiviral-immune-responses-by-targeting-deubiquitinase-usp19
#37
JOURNAL ARTICLE
Asela Weerawardhana, Thilina U B Herath, W A Gayan Chathuranga, Tae-Hwan Kim, Pathum Ekanayaka, Kiramage Chathuranga, Ho-Chul Kang, Jae U Jung, Jong-Soo Lee
Tight control of the type I interferon (IFN) signaling pathway is critical for maintaining host innate immune responses, and the ubiquitination and deubiquitination of signaling molecules are essential for signal transduction. Deubiquitinase ubiquitin-specific protein 19 (USP19) is known to be involved in deubiquitinating Beclin1, TRAF3, and TRIF for downregulation of the type I IFN signaling. Here, we show that SIAH1, a cellular E3 ubiquitin ligase that is involved in multicellular pathway, is a potent positive regulator of virus-mediated type I IFN signaling that maintains homeostasis within the antiviral immune response by targeting USP19...
March 2024: Journal of Medical Virology
https://read.qxmd.com/read/38481993/gonadal-androgens-are-associated-with-decreased-type-i-interferon-production-by-plasmacytoid-dendritic-cells-and-increased-igg-titres-to-bnt162b2-following-co-vaccination-with-live-attenuated-influenza-vaccine-in-adolescents
#38
JOURNAL ARTICLE
Oliver L Sampson, Cecilia Jay, Emily Adland, Anna Csala, Nicholas Lim, Stella M Ebbrecht, Lorna C Gilligan, Angela E Taylor, Sherley Sherafin George, Stephanie Longet, Lucy C Jones, Ellie Barnes, John Frater, Paul Klenerman, Susie Dunachie, Miles Carrol, James Hawley, Wiebke Arlt, Andreas Groll, Philip Goulder
mRNA vaccine technologies introduced following the SARS-CoV-2 pandemic have highlighted the need to better understand the interaction of adjuvants and the early innate immune response. Type I interferon (IFN-I) is an integral part of this early innate response that primes several components of the adaptive immune response. Women are widely reported to respond better than men to tri- and quadrivalent influenza vaccines. Plasmacytoid dendritic cells (pDCs) are the primary cell type responsible for IFN-I production, and female pDCs produce more IFN-I than male pDCs since the upstream pattern recognition receptor Toll-like receptor 7 (TLR7) is encoded by X chromosome and is biallelically expressed by up to 30% of female immune cells...
2024: Frontiers in Immunology
https://read.qxmd.com/read/38480836/universal-sting-mimic-boosts-antitumour-immunity-via-preferential-activation-of-tumour-control-signalling-pathways
#39
JOURNAL ARTICLE
Ying Wang, Sirui Li, Mengying Hu, Yuchen Yang, Ellie McCabe, Lillian Zhang, Andrew M Withrow, Jenny P-Y Ting, Rihe Liu
The efficacy of STING (stimulator of interferon genes) agonists is due to various factors, primarily inefficient intracellular delivery, low/lack of endogenous STING expression in many tumours, and a complex balance between tumour control and progression. Here we report a universal STING mimic (uniSTING) based on a polymeric architecture. UniSTING activates STING signalling in a range of mouse and human cell types, independent of endogenous STING expression, and selectively stimulates tumour control IRF3/IFN-I pathways, but not tumour progression NF-κB pathways...
March 13, 2024: Nature Nanotechnology
https://read.qxmd.com/read/38480499/apigenin-suppresses-innate-immune-responses-and-ameliorates-lipopolysaccharide-induced-inflammation-via-inhibition-of-sting-irf3-pathway
#40
JOURNAL ARTICLE
Xu-Wei Zhou, Juan Wang, Wen-Fu Tan
The stimulator of interferon genes (STING) signaling pathway is crucial for the pathogenesis of autoimmune and inflammatory disorders, including acute lung injury (ALI). Apigenin (4[Formula: see text],5,7-trihydroxyflavone) is a natural flavonoid widely found in fruits, vegetables, and Chinese medicinal herbs that exhibits a range of pharmacological effects, such as antibacterial and anti-inflammatory activities. However, the efficacy of apigenin in STING pathway-mediated diseases remains unclear. Accordingly, this study screened Chinese medicines to identify potent agents that reduced the synthesis of type I interferons (IFNs)...
March 14, 2024: American Journal of Chinese Medicine
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