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Interferon regulatory factor

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https://www.readbyqxmd.com/read/29346347/cd103-cd11b-mucosal-classical-dendritic-cells-initiate-long-term-switched-antibody-responses-to-flagellin
#1
A Flores-Langarica, K Müller Luda, E K Persson, C N Cook, S Bobat, J L Marshall, M W Dahlgren, K Hägerbrand, K M Toellner, M D Goodall, D R Withers, I R Henderson, B Johansson Lindbom, A F Cunningham, W W Agace
Antibody responses induced at mucosal and nonmucosal sites demonstrate a significant level of autonomy. Here, we demonstrate a key role for mucosal interferon regulatory factor-4 (IRF4)-dependent CD103+CD11b+ (DP), classical dendritic cells (cDCs) in the induction of T-dependent immunoglobulin G (IgG) and immunoglobulin A (IgA) responses in the mesenteric lymph node (MLN) following systemic immunization with soluble flagellin (sFliC). In contrast, IRF8-dependent CD103+CD11b- (SP) are not required for these responses...
December 20, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29346274/irf4-mediates-the-oncogenic-effects-of-stat3-in-anaplastic-large-cell-lymphomas
#2
Cecilia Bandini, Aldi Pupuleku, Elisa Spaccarotella, Elisa Pellegrino, Rui Wang, Nicoletta Vitale, Carlotta Duval, Daniela Cantarella, Andrea Rinaldi, Paolo Provero, Ferdinando Di Cunto, Enzo Medico, Francesco Bertoni, Giorgio Inghirami, Roberto Piva
Systemic anaplastic large cell lymphomas (ALCL) are a category of T-cell non-Hodgkin's lymphomas which can be divided into anaplastic lymphoma kinase (ALK) positive and ALK negative subgroups, based on ALK gene rearrangements. Among several pathways aberrantly activated in ALCL, the constitutive activation of signal transducer and activator of transcription 3 (STAT3) is shared by all ALK positive ALCL and has been detected in a subgroup of ALK negative ALCL. To discover essential mediators of STAT3 oncogenic activity that may represent feasible targets for ALCL therapies, we combined gene expression profiling analysis and RNA interference functional approaches...
January 18, 2018: Cancers
https://www.readbyqxmd.com/read/29343810/mitochondrial-dna-damage-and-subsequent-activation-of-z-dna-binding-protein-1-links-oxidative-stress-to-inflammation-in-epithelial-cells
#3
Bartosz Szczesny, Michela Marcatti, Akbar Ahmad, Mauro Montalbano, Attila Brunyánszki, Sofia-Iris Bibli, Andreas Papapetropoulos, Csaba Szabo
This report identifies mitochondrial DNA (mtDNA) as a target and active mediator that links low-level oxidative stress to inflammatory response in pulmonary epithelial cells. Extrusion of mtDNA into the bronchoalveolar lavage fluid occurs as an early event in mice subjected to cigarette smoke injury, concomitantly with the depletion of mtDNA in the lung tissue. In cultured lung epithelial cells, prolonged, low-level oxidative stress damages the mtDNA, without any detectable damage to the nuclear DNA. In turn, cellular depletion of the mtDNA occurs, together with a transient remodeling of cellular bioenergetics and morphology - all without any detectable impairment in overall cell viability...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29343584/human-herpesvirus-8-interferon-regulatory-factors-1-and-3-mediate-replication-and-latency-activities-via-interactions-with-usp7-deubiquitinase
#4
Qiwang Xiang, Hyunwoo Ju, Qian Li, Szu-Chieh Mei, Daming Chen, Young Bong Choi, John Nicholas
Human herpesvirus 8 (HHV-8) encodes four viral interferon regulatory factors (vIRFs 1-4) that likely function to suppress innate immune and cellular stress responses through inhibitory interactions with various cellular proteins involved in these activities. It is notable that vIRFs 1 and 4 have been reported to interact with the deubiquitinase USP7, substrates of which include p53 and p53-targeting and destabilizing ubiquitin E3 ligase MDM2. Structural studies of vIRF-1 and vIRF-4 USP7-binding sequences in association with USP7 have been reported; both involve interactions with N-terminal domain residues of USP7, via EGPS and ASTS motifs in vIRF-1 and vIRF-4, respectively, but vIRF-4 residues also contact the catalytic site...
January 17, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29339435/corrected-and-republished-from-the-cop9-signalosome-interacts-with-and-regulates-interferon-regulatory-factor-5-protein-stability
#5
Justyna Korczeniewska, Betsy J Barnes
The transcription factor interferon regulatory factor 5 (IRF5) exerts crucial functions in the regulation of host immunity against extracellular pathogens, DNA damage-induced apoptosis, death receptor signaling, and macrophage polarization. Tight regulation of IRF5 is thus warranted for an efficient response to extracellular stressors and for limiting autoimmune and inflammatory responses. Here we report that the COP9 signalosome (CSN), a general modulator of diverse cellular and developmental processes, associates constitutively with IRF5 and promotes its protein stability...
February 1, 2018: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29339432/deregulation-of-hdac5-by-viral-interferon-regulatory-factor-3-plays-an-essential-role-in-kaposi-s-sarcoma-associated-herpesvirus-induced-lymphangiogenesis
#6
Hye-Ra Lee, Fan Li, Un Yung Choi, Hye Ryun Yu, Grace M Aldrovandi, Pinghui Feng, Shou-Jiang Gao, Young-Kwon Hong, Jae U Jung
Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent for Kaposi's sarcoma (KS), which is one of the most common HIV-associated neoplasms. The endothelium is the thin layer of squamous cells where vascular blood endothelial cells (BECs) line the interior surface of blood vessels and lymphatic endothelial cells (LECs) are in direct contact with lymphatic vessels. The KS lesions contain a prominent compartment of neoplastic spindle morphology cells that are closely related to LECs. Furthermore, while KSHV can infect both LECs and BECs in vitro, its infection activates genetic programming related to lymphatic endothelial cell fate, suggesting that lymphangiogenic pathways are involved in KSHV infection and malignancy...
January 16, 2018: MBio
https://www.readbyqxmd.com/read/29339070/involvement-of-interferon-regulatory-factor-3-from-the-barbel-chub-squaliobarbus-curriculus-in-the-immune-response-against-grass-carp-reovirus
#7
Ronghua Wang, Yaoguo Li, Zhiyu Zhou, Qiaolin Liu, Lingbing Zeng, Tiaoyi Xiao
The barbel chub Squaliobarbus curriculus is an important commercial fish species in China, and has shown significant resistance to grass carp reovirus (GCRV). In this study, the cDNA sequence of interferon regulatory factors 3 (IRF3) from Squaliobarbus curriculus, designated as ScIRF3, was cloned, and its effect against GCRV was investigated. The full-length 1837 base pair (bp) cDNA of ScIRF3 contained a complete open reading frame of 1374 bp and encoded a putative polypeptide of 457 amino acid residues. The ScIRF3 protein contained conserved domains, including an N-terminal DNA-binding domain, a C-terminal IRF association domain, and a serine-rich domain...
January 12, 2018: Gene
https://www.readbyqxmd.com/read/29324236/irf1-up-regulates-isg15-gene-expression-in-dsrna-stimulation-or-csfv-infection-by-targeting-nucleotides-487-to-325-in-the-5-flanking-region
#8
Xiao-Quan Li, Xiao Ning Li, Jing-Jing Liang, Xin-Bin Cai, Qian Tao, Yu-Xiao Li, Qing Qin, Su-Ping Xu, Ting Rong Luo
Interferon (IFN)-stimulated gene 15 (ISG15) encodes a ubiquitin-like protein that is heavily involved in immune response elicitation. As an important member of interferon regulatory factor (IRF) family, IRF1 can activate the expression of multiple genes, including the human optineurin gene (Sudhakar et al., 2013). In this study, a sequence in the promoter region of the optineurin gene was compared to the 5' flanking region of the porcine isg15 gene. Porcine IRF1 also possesses antiviral activity against several swine viruses (Li et al...
January 8, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29317664/human-cytomegalovirus-encoded-us9-targets-mavs-and-sting-signaling-to-evade-type-i-interferon-immune-responses
#9
Hyun Jin Choi, Areum Park, Sujin Kang, Eunhye Lee, Taeyun A Lee, Eun A Ra, Jiseon Lee, Sungwook Lee, Boyoun Park
Human cytomegalovirus (HCMV) has evolved sophisticated immune evasion mechanisms that target both the innate and adaptive immune responses. However, how HCMV encoded proteins are involved in this immune escape is not clear. Here, we show that HCMV glycoprotein US9 inhibits the IFN-β response by targeting the mitochondrial antiviral-signaling protein (MAVS) and stimulator of interferon genes (STING)-mediated signaling pathways. US9 accumulation in mitochondria attenuates the mitochondrial membrane potential, leading to promotion of MAVS leakage from the mitochondria...
January 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/29316737/the-effect-of-lipopolysaccharide-on-noxa-expression-is-mediated-through-irf-1-3-and-7
#10
Sujan Piya, Tae-Hyoung Kim
Lipopolysaccharide (LPS), a component of the cell wall of gram-negative bacteria, elicits the secretion of cytokines, such as interferons, that stimulate the host defense system. Previously, we demonstrated that interferons induce interferon regulatory factors (IRFs) 1, 3, and 7 that regulate transcription of Noxa and alter expression profiles of Bcl-2 family proteins in tumors. However, the immediate consequences of LPS stimulation on Noxa and BH3 expression in tumor cells remain uncharacterized. Here, we determined that LPS induced Noxa expression in CT26 cells...
January 11, 2018: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29313175/a-biomolecular-network-driven-proteinic-interaction-in-hcv-clearance
#11
Pratichi Singh, Febin Prabhu Dass J
Hepatitis C virus infection causes chronic liver disease that leads to cancer-related mortality. Presently around 30% of the HCV (infected) affected population get rid of the infection through spontaneous disease clearance. This phenomenon is conducted by a set of reported immune candidate genes. Hence, this study focuses only on these immune-response related genes with aid of network approach, where the idea is to disseminate the network for better understanding of key functional genes and their transcription control activity...
January 8, 2018: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29311129/regulatory-t-cells-from-discovery-to-autoimmunity
#12
Alexandra Kitz, Emily Singer, David Hafler
Multiple sclerosis (MS) is a genetically mediated autoimmune disease of the central nervous system. Allelic variants lead to lower thresholds of T-cell activation resulting in activation of autoreactive T cells. Environmental factors, including, among others, diet, vitamin D, and smoking, in combination with genetic predispositions, play a substantial role in disease development and activation of autoreactive T cells. FoxP3+ regulatory T cells (Tregs) have emerged as central in the control of autoreactive T cells...
January 8, 2018: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/29298097/functional-defects-of-regulatory-t-cell-through-interleukin-10-mediated-mechanism-in-the-induction-of-gestational-diabetes-mellitus
#13
Yan Yang, Lixiu Liu, Beibei Liu, Qi Li, Zhe Wang, Sitong Fan, He Wang, Liandi Wang
Gestational diabetes mellitus (GDM) is a metabolic and low-grade inflammatory disease most commonly found in pregnant women with high body mass index and non-Caucasian ethnicities; however, not all women of high-risk groups develop GDM. We hypothesized that regulatory T cells (Tregs) might present a role in suppressing GDM development. To this end, 55 high-risk women at early pregnancy (first trimester) were recruited, and 21 of them developed GDM while the other 34 did not. Compared to those subjects who did not develop GDM (non-GDM), the patients who developed GDM presented reduced levels of Tregs and elevated levels of serum interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha)...
January 3, 2018: DNA and Cell Biology
https://www.readbyqxmd.com/read/29296736/novel-gm-csf-signals-via-ifn-%C3%AE-r-irf-1-and-akt-mtor-license-monocytes-for-suppressor-function
#14
Eliana Ribechini, James A Hutchinson, Sabine Hergovits, Marion Heuer, Jörg Lucas, Ulrike Schleicher, Ana-Laura Jordán Garrote, Sarah J Potter, Paloma Riquelme, Heike Brackmann, Nora Müller, Hartmann Raifer, Ingolf Berberich, Magdalena Huber, Andreas Beilhack, Michael Lohoff, Christian Bogdan, Matthias Eyrich, Heike M Hermanns, Edward K Geissler, Manfred B Lutz
Granulocyte-macrophage colony-stimulating factor (GM-CSF) controls proliferation and survival of myeloid cells including monocytes. Here, we describe a time-dependent licensing process driven by GM-CSF in murine Ly6Chigh and human CD14+ monocytes that disables their inflammatory functions and promotes their conversion into suppressor cells. This 2-step licensing of monocytes requires activation of the AKT/mTOR/mTORC1 signaling cascade by GM-CSF followed by signaling through the interferon-γ receptor (IFN-γR)/interferon regulatory factor-1 (IRF-1) pathway...
June 13, 2017: Blood Advances
https://www.readbyqxmd.com/read/29295954/blockade-of-tnfr2-signaling-enhances-the-immunotherapeutic-effect-of-cpg-odn-in-a-mouse-model-of-colon-cancer
#15
Yingjie Nie, Jiang He, Hidekazu Shirota, Anna L Trivett, De Yang, Dennis M Klinman, Joost J Oppenheim, Xin Chen
Through the tumor necrosis factor (TNF) receptor type II (TNFR2), TNF preferentially activates, expands, and promotes the phenotypic stability of CD4+Foxp3+ regulatory T (Treg) cells. Those Treg cells that have a high abundance of TNFR2 have the maximal immunosuppressive capacity. We investigated whether targeting TNFR2 could effectively suppress the activity of Treg cells and consequently enhance the efficacy of cancer immunotherapy. We found that, relative to a suboptimal dose of the immunostimulatory Toll-like receptor 9 ligand CpG oligodeoxynucleotide (ODN), the combination of the suboptimal dose of CpG ODN with the TNFR2-blocking antibody M861 more markedly inhibited the growth of subcutaneously grafted mouse CT26 colon tumor cells...
January 2, 2018: Science Signaling
https://www.readbyqxmd.com/read/29290284/oral-cancer-derived-exosomal-nap1-enhances-cytotoxicity-of-natural-killer-cells-via-the-irf-3-pathway
#16
Yingnan Wang, Xing Qin, Xueqin Zhu, Wanjun Chen, Jianjun Zhang, Wantao Chen
OBJECTIVE: To examine the effects of oral cancer-derived exosomes (OCEXs) on natural killer (NK) cells and to explore the underlying mechanism. MATERIALS AND METHODS: OCEXs were isolated from the cell culture supernatant of oral cancer (OC) cells using ultrafiltration and affinity chromatography and were identified using electron microscopy, nanoparticle tracking analysis (NTA) and immunoblotting. The effects of OCEXs on NK cells were analyzed using laser scanning confocal microscopy and several functional assays of NK cells...
January 2018: Oral Oncology
https://www.readbyqxmd.com/read/29285097/mir-34a-and-mir-125b-are-upregulated-in-peripheral-blood-mononuclear-cells-from-patients-with-type-2-diabetes-mellitus
#17
Yanxin Shen, Huiling Xu, Xiaoyuan Pan, Weijiang Wu, Hui Wang, Linlin Yan, Miaomiao Zhang, Xia Liu, Sheng Xia, Qixiang Shao
Type 2 diabetes mellitus (T2DM) is a leading cause of blindness, non-traumatic amputation and end-stage renal disease, as well as a major cardiovascular risk factor. To determine whether miR-125b and miR-34a serve an important role in the development of T2DM, the current study investigated the expression profile of two microRNAs (miR-34a and miR-125b) and their relative genes in peripheral blood mononuclear cells from 73 patients with T2DM and 52 healthy donors by reverse transcription-quantitative polymerase chain reaction In addition, the association between miR-34a, miR-125b and their relevant genes expression profile were analyzed with respect to the pathogenesis of T2DM...
December 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29285077/identification-of-micrornas-in-human-circulating-monocytes-of-postmenopausal-osteoporotic-mexican-mestizo-women-a-pilot-study
#18
Rogelio F Jiménez-Ortega, Eric G Ramírez-Salazar, Alma Y Parra-Torres, Said A Muñoz-Montero, Claudia Rangel-Escareňo, Ivan Salido-Guadarrama, Mauricio Rodriguez-Dorantes, Manuel Quiterio, Jorge Salmerón, Rafael Velázquez-Cruz
MicroRNAs (miRNAs or miRs) are a class of short non-coding RNAs that serve an important regulatory role in living organisms. These molecules are associated with multiple biological processes and are potential biomarkers in multiple diseases. The present study aimed to further identify miRNAs that are differentially expressed in circulating monocytes (CMCs) from postmenopausal Mexican-Mestizo women. Microarray analyses of monocytes using Affymetrix miRNA 4.0 and Human Genome U133 Plus 2.0 arrays were performed in 6 normal and 6 osteoporotic women, followed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) validation...
December 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29281764/interferon-regulatory-factor-1-is-essential-for-pathogenic-cd8-t-cell-migration-and-retention-in-the-brain-during-experimental-cerebral-malaria
#19
Sin Yee Gun, Carla Claser, Teck Hui Teo, Shanshan W Howland, Chek Meng Poh, Rebecca Ren Ying Chye, Lisa F P Ng, Laurent Rénia
Host immune response has a key role in controlling the progression of malaria infection. In the well-established murine model of experimental cerebral malaria (ECM) with P. berghei ANKA infection, pro-inflammatory Th1 and CD8+ T cells response are essential for disease development. Interferon regulatory factor 1 (IRF1) is a transcription factor which promotes Th1 responses and its absence was previously shown to protect from ECM death. Yet, the exact mechanism of protection remains unknown. Here we demonstrated that IRF1-deficient mice (IRF1KO) were protected from ECM death despite displaying early neurological signs...
December 27, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/29280433/cd45ro-t-cells-and-t-cell-activation-in-the-long-lasting-immunity-after-leishmania-infantum-infection
#20
João F Rodrigues-Neto, Gloria R Monteiro, Tatjana S L Keesen, Henio G Lacerda, Edgar M Carvalho, Selma M B Jeronimo
Manifestations of Leishmania infantum infection range from asymptomatic to symptomatic visceral leishmaniasis (VL). People with symptomatic VL (sVL) have suppressed immune responses against Leishmania antigens that are reversed after clinical cure. The intradermal leishmanin skin test (LST) is negative during sVL, but it becomes positive after treatment. The aim of this study was to compare T cell responses in individuals with sVL, recovered VL (RecVL), and endemic controls. Endemic controls were household contacts of a VL case and they were grouped by their LST results, either positive (LST+) or negative (LST-)...
December 26, 2017: American Journal of Tropical Medicine and Hygiene
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