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IRF4

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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/29339772/foxo1-promotes-th9-cell-differentiation-and-airway-allergy
#3
Thomas S Buttrick, Wei Wang, Christina Yung, Kenneth G Trieu, Kruti Patel, Samia J Khoury, Xingbin Ai, Wassim Elyaman
T helper 9 (Th9) cells are effector CD4+ T cells that are characterized by the production of interleukin-9 (IL-9) and have been associated with allergic responses. Here, we found that the expression of the transcription factor forkhead box O1 (Foxo1) was induced in Th9 and Foxo1 plays a crucial role in the differentiation of Th9 cells. Pharmacological inhibition of Foxo1 or genetic disruption of Foxo1 in CD4+ T cells caused a reduction in IL-9 expression while upregulating IL-17A and IFNγ production. Furthermore, chromatin immunoprecipitation (ChIP) followed by luciferase assays revealed direct binding of Foxo1 to both the Il9 and Irf4 promoters and induces their transactivation...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29317217/crucial-role-of-ho-1-irf4-dependent-apoptosis-induced-by-panobinostat-and-lenalidomide-in-multiple-myeloma
#4
Sishi Tang, Dan Ma, Bingqing Cheng, Qing Fang, Xinyi Kuang, Kunling Yu, Weili Wang, Bo Hu, Jishi Wang
Inhibition of histone deacetylase (HDAC) is a promising therapeutic strategy for various hematologic cancers. Panobinostat has been approved for treating patients with multiple myeloma (MM) by the FDA. Since the mechanism for the resistance of panobinostat to MM remains elusive, we aimed to clarify this mechanism and the synergism of panobinostat with lenalidomide. The mRNA and protein of transcription factor IRF4 were overexpressed in CD138+ mononuclear cells from MM patients compared with in those from healthy donors...
January 6, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29316737/the-effect-of-lipopolysaccharide-on-noxa-expression-is-mediated-through-irf-1-3-and-7
#5
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/29315480/iris-pigmented-lesions-as-a-marker-of-cutaneous-melanoma-risk-an-australian-case-control-study
#6
A M Laino, E G Berry, K Jagirdar, K J Lee, D L Duffy, H P Soyer, R A Sturm
BACKGROUND: Iris naevi and iris freckles have a frequency of 4% and 50% in the European population. They are associated with dysplastic naevi, but few studies examine their link to cutaneous melanoma. OBJECTIVES: To assess whether iris pigmented lesions are a predictive indicator for cutaneous melanoma. METHODS: This is a melanoma case-control study of 1254 European-background Australians. Sun exposure and melanoma history, a saliva sample for DNA analysis, and eye photographs taken with a digital camera were collected from 1117 participants...
January 8, 2018: British Journal of Dermatology
https://www.readbyqxmd.com/read/29313948/human-dendritic-cell-subsets-an-update
#7
REVIEW
Matthew Collin, Venetia Bigley
Dendritic cells (DC) are a class of bone marrow derived cells arising from lympho-myeloid haematopoiesis that form an essential interface between the innate sensing of pathogens and the activation of adaptive immunity. This task requires a wide range of mechanisms and responses, which are divided between three major DC subsets: plasmacytoid DC (pDC), myeloid/conventional DC1 (cDC1) and myeloid/conventional DC2 (cDC2). Each DC subset develops under the control of a specific repertoire of transcription factors involving differential levels of IRF8 and IRF4 in collaboration with PU...
January 3, 2018: Immunology
https://www.readbyqxmd.com/read/29311150/correction-irf4-dependent-cd103-cd11b-dendritic-cells-and-the-intestinal-microbiome-regulate-monocyte-and-macrophage-activation-and-intestinal-peristalsis-in-postoperative-ileus
#8
https://www.readbyqxmd.com/read/29296880/cd86-regulates-myeloma-cell-survival
#9
Catherine M Gavile, Benjamin G Barwick, Scott Newman, Paola Neri, Ajay K Nooka, Sagar Lonial, Kelvin P Lee, Lawrence H Boise
Although prognosis for patients with multiple myeloma has improved over the past decade, research toward discovery of new therapeutic avenues is important and could lead to a cure for this plasma cell malignancy. Here we show that blocking the CD28-CD86 pathway via silencing of either CD28 or CD86 leads to myeloma cell death. Inhibiting this pathway leads to downregulation of integrins and IRF4, a known myeloma survival factor. Our data also indicate that CD86, the canonical ligand in this pathway, has prosurvival activity that is dependent on its cytosolic domain...
November 28, 2017: Blood Advances
https://www.readbyqxmd.com/read/29284783/cd150-and-cd180-are-involved-in-regulation-of-transcription-factors-expression-in-chronic-lymphocytic-leukemia-cells
#10
I Gordiienko, L Shlapatska, V M Kholodniuk, L Kovalevska, T S Ivanivskaya, S P Sidorenko
BACKGROUND: Sequential stages of B-cell development is stringently coordinated by transcription factors (TFs) network that include B-lineage commitment TFs (Ikaros, Runx1/Cbfb, E2A, and FOXO1), B-lineage maintenance TFs (EBF1 and PAX5) and stage specific set of TFs (IRF4, IRF8, BCL6, BLIMP1). Deregulation of TFs expression and activity is often occurs in malignant B cells. The aim of this study was to evaluate TFs expression in chronic lymphocytic leukemia cells taking into consideration CD150 cell surface expression...
December 2017: Experimental Oncology
https://www.readbyqxmd.com/read/29262341/feeling-exhausted-tuning-irf4-energizes-dysfunctional-t-cells
#11
Vijaykumar Chennupati, Werner Held
The regulatory mechanisms governing T cell exhaustion remain incompletely understood. Man et al. (2017) and Wu et al. (2017) report that the T cell receptor responsive transcription factor Irf4 promotes T cell exhaustion in chronic viral infection but dampens exhaustion in response to tissue allografts.
December 19, 2017: Immunity
https://www.readbyqxmd.com/read/29251015/prognostic-impact-of-activation-induced-cytidine-deaminase-expression-for-patients-with-diffuse-large-b-cell-lymphoma
#12
Hiroshi Arima, Masakazu Fujimoto, Momoko Nishikori, Toshiyuki Kitano, Wataru Kishimoto, Masakatsu Hishizawa, Tadakazu Kondo, Kouhei Yamashita, Masahiro Hirata, Hironori Haga, Akifumi Takaori-Kondo
Activation-induced cytidine deaminase (AID) plays important roles in the development of diffuse large B-cell lymphoma (DLBCL); however, its prognostic value remains controversial. Here, we evaluated AID expression in 71 DLBCL patients treated with R-CHOP by immunohistochemistry and investigated its prognostic significance. AID expression was detected in 40.8% of DLBCL samples and associated with IRF4 expression. Notably, AID expression correlated with shorter progression-free survival and overall survival for patients with high (3-5) international prognostic index (IPI) score...
December 18, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29246443/transcription-factor-irf4-promotes-cd8-t-cell-exhaustion-and-limits-the-development-of-memory-like-t-cells-during-chronic-infection
#13
Kevin Man, Sarah S Gabriel, Yang Liao, Renee Gloury, Simon Preston, Darren C Henstridge, Marc Pellegrini, Dietmar Zehn, Friederike Berberich-Siebelt, Mark A Febbraio, Wei Shi, Axel Kallies
During chronic stimulation, CD8+ T cells acquire an exhausted phenotype characterized by expression of inhibitory receptors, down-modulation of effector function, and metabolic impairments. T cell exhaustion protects from excessive immunopathology but limits clearance of virus-infected or tumor cells. We transcriptionally profiled antigen-specific T cells from mice infected lymphocytic choriomeningitis virus strains that cause acute or chronic disease. T cell exhaustion during chronic infection was driven by high amounts of T cell receptor (TCR)-induced transcription factors IRF4, BATF, and NFATc1...
December 11, 2017: Immunity
https://www.readbyqxmd.com/read/29233972/irf8-dependent-molecular-complexes-control-the-th9-transcriptional-program
#14
Etienne Humblin, Marion Thibaudin, Fanny Chalmin, Valentin Derangère, Emeric Limagne, Corentin Richard, Richard A Flavell, Sandy Chevrier, Sylvain Ladoire, Hélène Berger, Romain Boidot, Lionel Apetoh, Frédérique Végran, François Ghiringhelli
Interferon regulatory factors (IRF) have critical functions in lymphoid development and in immune response regulation. Although many studies have described the function of IRF4 in CD4+ T cells, few have focused on the IRF4 homologue, IRF8. Here, we show that IRF8 is required for Th9 differentiation in vitro and in vivo. IRF8 functions through a transcription factor complex consisting of IRF8, IRF4, PU.1 and BATF, which binds to DNA and boosts Il9 transcription. By contrast, IRF8 deficiency promotes the expression of other genes such as Il4, as IRF8 dimerises with the transcriptional repressor ETV6 and inhibits Il4 expression...
December 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/29221730/ablation-of-transcription-factor-irf4-promotes-transplant-acceptance-by-driving-allogenic-cd4-t-cell-dysfunction
#15
Jie Wu, Hedong Zhang, Xiaomin Shi, Xiang Xiao, Yihui Fan, Laurie J Minze, Jin Wang, Rafik M Ghobrial, Jiahong Xia, Roger Sciammas, Xian C Li, Wenhao Chen
CD4+ T cells orchestrate immune responses and destruction of allogeneic organ transplants, but how this process is regulated on a transcriptional level remains unclear. Here, we demonstrated that interferon regulatory factor 4 (IRF4) was a key transcriptional determinant controlling T cell responses during transplantation. IRF4 deletion in mice resulted in progressive establishment of CD4+ T cell dysfunction and long-term allograft survival. Mechanistically, IRF4 repressed PD-1, Helios, and other molecules associated with T cell dysfunction...
December 4, 2017: Immunity
https://www.readbyqxmd.com/read/29215541/pancreatic-insufficiency-in-cystic-fibrosis-influence-of-inflammatory-response-genes
#16
Fernando Augusto Lima Marson, Carmen Sílvia Bertuzzo, Tânia Kawasaki de Araujo, Taís Daiene Russo Hortencio, Antônio Fernando Ribeiro, José Dirceu Ribeiro
OBJECTIVE: Pancreatic insufficiency (PI) in cystic fibrosis (CF) patients is a crucial clinical marker for severity and disease progression. In our study, 125 modifier genes and their SNPs were associated between CF patients with PI or pancreatic sufficiency. METHODS: We prospectively evaluated 214 CF patients admitted at 1 hospital for a 2-year period. The PI status was associated with clinical variables and SNPs related with inflammatory response considering CFTR mutations...
December 5, 2017: Pancreas
https://www.readbyqxmd.com/read/29212740/il-23-interleukin-23-producing-conventional-dendritic-cells-control-the-detrimental-il-17-interleukin-17-response-in-stroke
#17
Mathias Gelderblom, Mattia Gallizioli, Peter Ludewig, Vivien Thom, Priyadharshini Arunachalam, Björn Rissiek, Christian Bernreuther, Markus Glatzel, Thomas Korn, Thiruma Valavan Arumugam, Jan Sedlacik, Christian Gerloff, Eva Tolosa, Anna M Planas, Tim Magnus
BACKGROUND AND PURPOSE: Inflammatory mechanisms can exacerbate ischemic tissue damage and worsen clinical outcome in patients with stroke. Both αβ and γδ T cells are established mediators of tissue damage in stroke, and the role of dendritic cells (DCs) in inducing the early events of T cell activation and differentiation in stroke is not well understood. METHODS: In a murine model of experimental stroke, we defined the immune phenotype of infiltrating DC subsets based on flow cytometry of surface markers, the expression of ontogenetic markers, and cytokine levels...
December 6, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/29196450/migratory-cd11b-conventional-dendritic-cells-induce-t-follicular-helper-cell-dependent-antibody-responses
#18
Jayendra Kumar Krishnaswamy, Uthaman Gowthaman, Biyan Zhang, Johan Mattsson, Louis Szeponik, Dong Liu, Renee Wu, Theresa White, Samuele Calabro, Lan Xu, Magalie A Collet, Marina Yurieva, Samuel Alsén, Per Fogelstrand, Anne Walter, William R Heath, Scott N Mueller, Ulf Yrlid, Adam Williams, Stephanie C Eisenbarth
T follicular helper (Tfh) cells are a subset of CD4+ T cells that promote antibody production during vaccination. Conventional dendritic cells (cDCs) efficiently prime Tfh cells; however, conclusions regarding which cDC instructs Tfh cell differentiation have differed between recent studies. We found that these discrepancies might exist because of the unusual sites used for immunization in murine models, which differentially bias which DC subsets access antigen. We used intranasal immunization as a physiologically relevant route of exposure that delivers antigen to all tissue DC subsets...
December 1, 2017: Science Immunology
https://www.readbyqxmd.com/read/29190509/genetic-determinants-of-freckle-occurrence-in-the-spanish-population-towards-ephelides-prediction-from-human-dna-samples
#19
Barbara Hernando, Maria Victoria Ibañez, Julio Alberto Deserio-Cuesta, Raquel Soria-Navarro, Inca Vilar-Sastre, Conrado Martinez-Cadenas
Prediction of human pigmentation traits, one of the most differentiable externally visible characteristics among individuals, from biological samples represents a useful tool in the field of forensic DNA phenotyping. In spite of freckling being a relatively common pigmentation characteristic in Europeans, little is known about the genetic basis of this largely genetically determined phenotype in southern European populations. In this work, we explored the predictive capacity of eight freckle and sunlight sensitivity-related genes in 458 individuals (266 non-freckled controls and 192 freckled cases) from Spain...
November 23, 2017: Forensic Science International. Genetics
https://www.readbyqxmd.com/read/29180032/composition-and-transcription-of-all-interferon-regulatory-factors-irfs-irf1%C3%A2-11-in-a-perciform-fish-the-mandarin-fish-siniperca-chuatsi
#20
Zubair Ahmed Laghari, Li Li, Shan Nan Chen, Hui Jun Huo, Bei Huang, Ying Zhou, P Nie
Interferon regulatory factors (IRFs) are a family of mediators in various biological processes including immune modulation of interferon (IFN) and proinflammatory cytokine expression. However, the data on the complete composition of IRFs is rather limited in teleost fish. In the present study, all IRF members, i.e. IRF1‒11 with two IRF4, IRF4a and IRF4b have been characterised in an aquaculture species of fish, the mandarin fish, Siniperca chuatsi, in addition to the previous report of IRF1, IRF2, IRF3 and IRF7 from the fish...
November 24, 2017: Developmental and Comparative Immunology
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