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https://www.readbyqxmd.com/read/28930664/aryl-hydrocarbon-receptor-controls-monocyte-differentiation-into-dendritic-cells-versus-macrophages
#1
Christel Goudot, Alice Coillard, Alexandra-Chloé Villani, Paul Gueguen, Adeline Cros, Siranush Sarkizova, Tsing-Lee Tang-Huau, Mylène Bohec, Sylvain Baulande, Nir Hacohen, Sebastian Amigorena, Elodie Segura
After entering tissues, monocytes differentiate into cells that share functional features with either macrophages or dendritic cells (DCs). How monocyte fate is directed toward monocyte-derived macrophages (mo-Macs) or monocyte-derived DCs (mo-DCs) and which transcription factors control these differentiation pathways remains unknown. Using an in vitro culture model yielding human mo-DCs and mo-Macs closely resembling those found in vivo in ascites, we show that IRF4 and MAFB were critical regulators of monocyte differentiation into mo-DCs and mo-Macs, respectively...
September 19, 2017: Immunity
https://www.readbyqxmd.com/read/28930660/the-irf4-gene-regulatory-module-functions-as-a-read-write-integrator-to-dynamically-coordinate-t%C3%A2-helper-cell-fate
#2
Veena Krishnamoorthy, Sunil Kannanganat, Mark Maienschein-Cline, Sarah L Cook, Jianjun Chen, Neil Bahroos, Evelyn Sievert, Emily Corse, Anita Chong, Roger Sciammas
Transcriptional regulation during CD4(+) T cell fate decisions enables their differentiation into distinct states, guiding immune responses toward antibody production via Tfh cells or inflammation by Teff cells. Tfh-Teff cell fate commitment is regulated by mutual antagonism between the transcription factors Bcl6 and Blimp-1. Here we examined how T cell receptor (TCR) signals establish and arbitrate Bcl6-Blimp-1 counter-antagonism. We found that the TCR-signal-induced transcription factor Irf4 is essential for the differentiation of Bcl6-expressing Tfh and Blimp-1-expressing Teff cells...
September 19, 2017: Immunity
https://www.readbyqxmd.com/read/28928075/expression-and-functional-characterization-of-interferon-regulatory-factors-4-8-and-9-in-large-yellow-croaker-larimichthys-crocea
#3
Jingteng Tang, Lihua Jiang, Wei Liu, Bao Lou, Changwen Wu, Jianshe Zhang
Interferon regulatory factor (IRF)-4, 8, and 9 are essential in host defense against pathogens. Here, the full-length coding sequence (CDS), protein structure, and immune response of IRF4/8/9 (lc IRF4/8/9) were characterized in large yellow croaker (Larimichthys crocea). The open reading frame of lcIRF4, lcIRF8 and lcIRF9 encoded putative proteins of 463,422 and 406 amino acids, respectively. These IRFs share high sequence homology with other vertebrate IRFs and were constitutively expressed in all examined tissues...
September 16, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28910419/il-10-mediated-signals-act-as-a-switch-for-lymphoproliferation-in-human-t-cell-leukemia-virus-type-1-infection-by-activating-the-stat3-and-irf4-pathways
#4
Leila Sawada, Yoshiko Nagano, Atsuhiko Hasegawa, Hikari Kanai, Kai Nogami, Sayaka Ito, Tomoo Sato, Yoshihisa Yamano, Yuetsu Tanaka, Takao Masuda, Mari Kannagi
Human T-cell leukemia virus type-1 (HTLV-1) causes two distinct diseases, adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Since there are no disease-specific differences among HTLV-1 strains, the etiological mechanisms separating these respective lymphoproliferative and inflammatory diseases are not well understood. In this study, by using IL-2-dependent HTLV-1-infected T-cell lines (ILTs) established from patients with ATL and HAM/TSP, we demonstrate that the anti-inflammatory cytokine IL-10 and its downstream signals potentially act as a switch for proliferation in HTLV-1-infected cells...
September 14, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28905935/age-related-differences-in-interferon-regulatory-factor-4-and-5-signaling-in-ischemic-brains-of-mice
#5
Shou-Cai Zhao, Chun Wang, Heng Xu, Wen-Qian Wu, Zhao-Hu Chu, Ling-Song Ma, Ying-Dong Zhang, Fudong Liu
Stroke is a disease that mainly affects the elderly. Since the age-related differences in stroke have not been well studied, modeling stroke in aged animals is clinically more relevant. The inflammatory responses to stroke are a fundamental pathological procedure, in which microglial activation plays an important role. Interferon regulatory factor-5 (IRF5) and IRF4 regulate M1 and M2 activation of macrophages, respectively, in peripheral inflammation; but it is unknown whether IRF5/IRF4 are also involved in cerebral inflammatory responses to stroke and whether age-related differences of the IRF5/IRF4 signaling exist in ischemic brain...
September 14, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28893954/the-orphan-nuclear-receptor-nr4a3-is-involved-in-the-function-of-dendritic-cells
#6
Masanori Nagaoka, Takuya Yashiro, Yuna Uchida, Tomoaki Ando, Mutsuko Hara, Hajime Arai, Hideoki Ogawa, Ko Okumura, Kazumi Kasakura, Chiharu Nishiyama
NR4A3/NOR1 belongs to the NR4A subfamily of the nuclear hormone receptor superfamily, which is activated in a ligand-independent manner. To examine the role of NR4A3 in gene expression of dendritic cells (DCs), we introduced NR4A3 small interfering RNA (siRNA) into bone marrow-derived DCs and determined the expression levels of mRNA and proteins of cytokines, cell surface molecules, NF-κB signaling-related proteins, and transcription factors. The expression level of NR4A3 was markedly upregulated by TLR-mediated stimulation in DCs...
September 11, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28889989/the-tnf-receptor-superfamily-nf-%C3%AE%C2%BAb-axis-is-critical-to-maintain-effector-regulatory-t-cells-in-lymphoid-and-non-lymphoid-tissues
#7
Ajithkumar Vasanthakumar, Yang Liao, Peggy Teh, Maria F Pascutti, Anna E Oja, Alexandra L Garnham, Renee Gloury, Jessica C Tempany, Tom Sidwell, Eloy Cuadrado, Paul Tuijnenburg, Taco W Kuijpers, Najoua Lalaoui, Lisa A Mielke, Vanessa L Bryant, Philip D Hodgkin, John Silke, Gordon K Smyth, Martijn A Nolte, Wei Shi, Axel Kallies
After exiting the thymus, Foxp3(+) regulatory T (Treg) cells undergo further differentiation in the periphery, resulting in the generation of mature, fully suppressive effector (e)Treg cells in a process dependent on TCR signaling and the transcription factor IRF4. Here, we show that tumor necrosis factor receptor superfamily (TNFRSF) signaling plays a crucial role in the development and maintenance of eTreg cells. TNFRSF signaling activated the NF-κB transcription factor RelA, which was required to maintain eTreg cells in lymphoid and non-lymphoid tissues, including RORγt(+) Treg cells in the small intestine...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28884089/splenic-microrna-expression-profiles-and-integration-analyses-involved-in-host-responses-to-salmonella-enteritidis-infection-in-chickens
#8
Peng Li, Wenlei Fan, Qinghe Li, Jie Wang, Ranran Liu, Nadia Everaert, Jie Liu, Yonghong Zhang, Maiqing Zheng, Huanxian Cui, Guiping Zhao, Jie Wen
To understand the role of miRNAs in regulating genes involved in the host response to Salmonella enteritidis (SE) infection, next generation sequencing was applied to explore the altered splenic expression of microRNAs (miRNAs) and deregulated genes in specific-pathogen-free chickens. Birds were either infected or not (controls, C) and those challenged with SE were evaluated 24 h later and separated into two groups on the basis of the severity of clinical symptoms and blood load of SE: resistant (R, SE challenged-slight clinical symptoms and <10(5) cfu / 10 μL), and susceptible (S, SE challenged-severe clinical symptoms and >10(7) cfu/10 μL)...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28869081/differential-regulation-of-il-23-production-in-m1-macrophages-by-tir8-sigirr-through-tlr4-or-tlr7-8-mediated-signaling
#9
Rui Yamaguchi, Arisa Sakamoto, Takatoshi Yamamoto, Shinji Narahara, Hiroyuki Sugiuchi, Yasuo Yamaguchi
Cross-talks between toll-like receptors (TLRs) including various negative regulatory mechanisms are many unknown. We investigated the differential mechanism of IL-23 production in M1 macrophages by single immunoglobulin interleukin-1 receptor-related (SIGIRR) molecule through TLR4 or TLR7/8. IL-12p40 production by M1 macrophages pretreated with human neutrophil elastase (HNE) was synergistically enhanced IL-12p40, but not IL-23 production, after exposure to lipopolysaccharide (LPS). LPS (a TLR4 agonist) induced a slight increase of IL-23 production, while Resiquimod (a TLR7/8 agonist) significantly enhanced IL-23 production...
August 28, 2017: Cytokine
https://www.readbyqxmd.com/read/28851732/interferon-regulatory-factor-4-inhibits-neointima-formation-by-engaging-klf4-signaling
#10
Wen-Lin Cheng, Zhi-Gang She, Juan-Juan Qin, Jun-Hong Guo, Fu-Han Gong, Peng Zhang, Chun Fang, Song Tian, Xue-Yong Zhu, Jun Gong, Zhi-Hua Wang, Zan Huang, Hongliang Li
Background -The mechanisms underlying neointima formation remain unclear. Interferon regulatory factors (IRFs), which are key innate immune regulators, play important roles in cardiometabolic diseases. However, the function of IRF4 in arterial restenosis is unknown. Methods -IRF4 expression was first detected in human and mouse restenotic arteries. Then, the effects of IRF4 on neointima formation were evaluated using universal IRF4-deficient mouse and rat carotid artery injury models. We performed immunostaining to identify IRF4-expressing cells in the lesions...
August 29, 2017: Circulation
https://www.readbyqxmd.com/read/28851699/an-aberrant-notch2-bcr-signaling-axis-in-b-cells-from-patients-with-chronic-gvhd
#11
Jonathan C Poe, Wei Jia, Hsuan Su, Sarah Anand, Jeremy J Rose, Prasanthi V Tata, Amy N Suthers, Corbin D Jones, Pei Fen Kuan, Benjamin G Vincent, Jonathan S Serody, Mitchell E Horwitz, Vincent T Ho, Steven Z Pavletic, Frances T Hakim, Kouros Owzar, Dadong Zhang, Bruce R Blazar, Christian W Siebel, Nelson J Chao, Ivan Maillard, Stefanie Sarantopoulos
B Cell Receptor (BCR)-activated B cells contribute to pathogenesis in chronic graft-versus-host disease (cGVHD), a condition manifested by both B cell autoreactivity and immune deficiency. We hypothesized that constitutive BCR activation precluded functional B cell maturation in cGVHD. To address this, we examined BCR-NOTCH2 synergy, since Notch has been shown to increase BCR responsiveness in normal mouse B cells. We conducted ex vivo activation and signaling assays of 30 primary samples from HCT patients with and without cGVHD...
August 29, 2017: Blood
https://www.readbyqxmd.com/read/28814673/human-lung-tumor-foxp3-tregs-upregulate-four-treg-locking-transcription-factors
#12
Tatiana Akimova, Tianyi Zhang, Dmitri Negorev, Sunil Singhal, Jason Stadanlick, Abhishek Rao, Michael Annunziata, Matthew H Levine, Ulf H Beier, Joshua M Diamond, Jason D Christie, Steven M Albelda, Evgeniy B Eruslanov, Wayne W Hancock
Experimental data indicate that FOXP3+ Tregs can markedly curtail host antitumor immune responses, but the properties of human intratumoral Tregs are still largely unknown, in part due to significant methodologic problems. We studied the phenotypic, functional, epigenetic, and transcriptional features of Tregs in 92 patients with non-small-cell lung cancer, comparing the features of Tregs within tumors versus corresponding blood, lung, and lymph node samples. Intratumoral Treg numbers and suppressive function were significantly increased compared with all other sites but did not display a distinctive phenotype by flow cytometry...
August 17, 2017: JCI Insight
https://www.readbyqxmd.com/read/28808358/mbd2-regulates-th17-cell-differentiation-and-experimental-severe-asthma-by-affecting-irf4-expression
#13
Aijun Jia, Yueling Wang, Wenjin Sun, Bing Xiao, Yan Wei, Lulu Qiu, Lin Mu, Li Xu, Jianmin Li, Xiufeng Zhang, Da Liu, Cong Peng, Dongshan Zhang, Xudong Xiang
Th17 cells and IL-17 participate in airway neutrophil infiltration characteristics in the pathogenesis of severe asthma. Methyl-CpG binding domain protein 2 (MBD2) expression increased in CD4(+) T cells in peripheral blood samples of asthma patients. However, little is known about that epigenetic regulation of MBD2 in both immunological pathogenesis of experimental severe asthma and CD4(+) T cell differentiation. Here, we established a neutrophil-predominant severe asthma model, which was characterized by airway hyperresponsiveness (AHR), BALF neutrophil granulocyte (NEU) increase, higher NEU and IL-17 protein levels, and more Th17 cell differentiation...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28802050/distinct-dc-subsets-regulate-adaptive-th1-and-2-responses-during-trichuris-muris-infection
#14
M Demiri, K Müller-Luda, W W Agace, M Svensson-Frej
Low- and high-dose infections with the murine large intestinal nematode Trichuris muris are associated with induction of adaptive Th1 and Th2 responses, respectively, in mesenteric lymph nodes (MLN). Classical dendritic cells (cDC) accumulate in the large intestinal mucosa and MLN upon T. muris infection, yet their role in driving adaptive responses to infection remains largely unknown. We performed low- and high-dose T. muris infections of mice deficient in defined cDC subsets to investigate their role in induction of adaptive immune responses...
August 12, 2017: Parasite Immunology
https://www.readbyqxmd.com/read/28791349/ubiquitin-specific-peptidase-4-stabilizes-interferon-regulatory-factor-protein-and-promotes-its-function-to-facilitate-interleukin-4-expression-in-t-helper-type-2-cells
#15
Zhixiang Guo, Peng Xu, Shangqing Ge, Chengxin Zhang, Xiaoyan Zheng, Jinguo Xu, Zhuang Liu, Bin Li, Shenglin Ge
We speculated that ubiquitin specific peptidase 4 (USP4) may deubiquitinate interferon regulatory factor 4 (IRF4) and affect T helper type 2 (Th2) cell function. This study aimed to validate this hypothesis. Here, the interaction between USP4 and IRF4 were analyzed by co-immunoprecipitation assay. The deubiquitin effect of USP4 on IRF4 was analyzed by the Ni-NTA pull down assay. Luciferase reporter gene constructs were used to analyze the effects of USP4, IRF4 and nuclear factor of activated T cell-2 (NFATc2) on the activation of the interleukin-4 (IL-4) promoter...
October 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28755520/genetic-variation-in-irf4-expression-modulates-growth-characteristics-tyrosinase-expression-and-interferon-gamma-response-in-melanocytic-cells
#16
Yash Chhabra, Hilary X L Yong, Mitchell E Fane, Arish Soogrim, Wen Lim, Dayana Nur Mahiuddin, Reuben S Q Kim, Melinda Ashcroft, Scott A Beatson, Stephen A Ainger, Darren J Smit, Kasturee Jagirdar, Graeme J Walker, Richard A Sturm, Aaron G Smith
A SNP within intron4 of the Interferon Regulatory Factor4 (IRF4) gene, rs12203592*C/T has been independently associated with pigmentation and age-specific effects on nevus count in European-derived populations. We have characterised the cis-regulatory activity of this intronic region and using human foreskin-derived melanoblast strains we have explored the correlation between IRF4 rs12203592 homozygous C/C and T/T genotypes with TYR enzyme activity, supporting its association with pigmentation traits. Further, higher IRF4 protein levels directed by the rs12203592*C allele were associated with increased basal proliferation but decreased cell viability following UVR, an etiological factor in melanoma development...
July 29, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/28751557/the-bet-bromodomain-inhibitor-cpi203-improves-lenalidomide-and-dexamethasone-activity-in-in-vitro-and-in-vivo-models-of-multiple-myeloma-by-blockade-of-ikaros-and-myc-signaling
#17
Tania Díaz, Vanina Rodríguez, Ester Lozano, Mari-Pau Mena, Marcos Calderón, Laura Rosiñol, Antonio Martínez, Natalia Tovar, Patricia Pérez-Galán, Joan Bladé, Gaël Roué, Carlos Fernández de Larrea
Most of patients with multiple myeloma treated with current therapies, including immunomodulatory drugs, eventually develop relapsed/refractory disease. Clinical activity of lenalidomide relies on degradation of Ikaros and the consequently reduction on IRF4 expression, both required for myeloma cell survival and involved in the regulation of MYC transcription. Thus, we sought to determine the combinatorial effect of a MYC-interfering therapy with lenalidomide/dexamethasone. We analyzed the potential therapeutic effect of the combination of BET bromodomain inhibitor CPI203 with the lenalidomide/dexamethasone regimen in myeloma cell lines...
July 27, 2017: Haematologica
https://www.readbyqxmd.com/read/28738086/an-essential-ebv-latent-antigen-3c-binds-bcl6-for-targeted-degradation-and-cell-proliferation
#18
Yonggang Pei, Shuvomoy Banerjee, Hem Chandra Jha, Zhiguo Sun, Erle S Robertson
The latent EBV nuclear antigen 3C (EBNA3C) is required for transformation of primary human B lymphocytes. Most mature B-cell malignancies originate from malignant transformation of germinal center (GC) B-cells. The GC reaction appears to have a role in malignant transformation, in which a major player of the GC reaction is Bcl6, a key regulator of this process. We now demonstrate that EBNA3C contributes to B-cell transformation by targeted degradation of Bcl6. We show that EBNA3C can physically associate with Bcl6...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28733463/tlr4-and-c5ar-crosstalk-in-dendritic-cells-induces-a-core-regulatory-network-of-rsk2-pi3k%C3%AE-sgk1-and-foxo-transcription-factors
#19
Anouk Zaal, Benjamin Nota, Kat S Moore, Miranda Dieker, S Marieke van Ham, Anja Ten Brinke
Crosstalk between complement component 5a receptors (C5aRs) and TLRs in dendritic cells (DCs) occurs upon pathogen invasion; however, studies on C5aR and TLR crosstalk mainly focused on the modulating effect of C5a on TLR-induced cytokine production. To elucidate the breadth of C5aR and TLR4 crosstalk, the effect of simultaneous treatment with C5a and LPS was investigated in human monocyte-derived DCs (moDCs) 2 h after stimulation using whole transcriptome sequencing analysis. Although the effect of C5a on hallmark genes defining TLR4-induced DC maturation was limited at this time point, RNA sequencing analysis revealed a great variety of novel C5a targets, of which many interfere with TLR4-mediated immune activation...
July 21, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28723546/local-modulation-of-antigen-presenting-cell-development-after-resolution-of-pneumonia-induces-long-term-susceptibility-to-secondary-infections
#20
Antoine Roquilly, Hamish E G McWilliam, Cedric Jacqueline, Zehua Tian, Raphael Cinotti, Marie Rimbert, Linda Wakim, Irina Caminschi, Mireille H Lahoud, Gabrielle T Belz, Axel Kallies, Justine D Mintern, Karim Asehnoune, Jose A Villadangos
Lung infections cause prolonged immune alterations and elevated susceptibility to secondary pneumonia. We found that, after resolution of primary viral or bacterial pneumonia, dendritic cells (DC), and macrophages exhibited poor antigen-presentation capacity and secretion of immunogenic cytokines. Development of these "paralyzed" DCs and macrophages depended on the immunosuppressive microenvironment established upon resolution of primary infection, which involved regulatory T (Treg) cells and the cytokine TGF-β...
July 18, 2017: Immunity
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