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https://www.readbyqxmd.com/read/28187197/genetic-variants-alter-t-bet-binding-and-gene-expression-in-mucosal-inflammatory-disease
#1
Katrina Soderquest, Arnulf Hertweck, Claudia Giambartolomei, Stephen Henderson, Rami Mohamed, Rimma Goldberg, Esperanza Perucha, Lude Franke, Javier Herrero, Vincent Plagnol, Richard G Jenner, Graham M Lord
The polarization of CD4+ T cells into distinct T helper cell lineages is essential for protective immunity against infection, but aberrant T cell polarization can cause autoimmunity. The transcription factor T-bet (TBX21) specifies the Th1 lineage and represses alternative T cell fates. Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) that may be causative for autoimmune diseases. The majority of these polymorphisms are located within non-coding distal regulatory elements...
February 10, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28139755/genetically-determined-high-activity-of-il-12-and-il-18-in-ulcerative-colitis-and-tlr5-in-crohns-disease-were-associated-with-non-response-to-anti-tnf-therapy
#2
S Bank, P S Andersen, J Burisch, N Pedersen, S Roug, J Galsgaard, S Y Turino, J B Brodersen, S Rashid, B K Rasmussen, S Avlund, T B Olesen, H J Hoffmann, B A Nexø, J Sode, U Vogel, V Andersen
Anti-tumour necrosis factor-α (TNF-α) is used for treatment of severe cases of inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). However, one-third of the patients do not respond to the treatment. A recent study indicated that genetically determined high activity of pro-inflammatory cytokines, including interleukin-1β (IL-1β), IL-6 and interferon gamma (IFN-γ), are associated with non-response to anti-TNF therapy. Using a candidate gene approach, 21 functional single-nucleotide polymorphisms (SNPs) in 14 genes in the Toll-like receptors, the inflammasome and the IFNG pathways were assessed in 482 and 256 prior anti-TNF naïve Danish patients with CD and UC, respectively...
January 31, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28057268/control-of-neuronal-development-by-t-box-genes-in-the-brain
#3
A B Mihalas, R F Hevner
T-box transcription factors play key roles in the regulation of developmental processes such as cell differentiation and migration. Mammals have 17 T-box genes, of which several regulate brain development. The Tbr1 subfamily of T-box genes is particularly important in development of the cerebral cortex, olfactory bulbs (OBs), and cerebellum. This subfamily is comprised of Tbr1, Tbr2 (also known as Eomes), and Tbx21. In developing cerebral cortex, Tbr2 and Tbr1 are expressed during successive stages of differentiation in the pyramidal neuron lineage, from Tbr2+ intermediate progenitors to Tbr1+ postmitotic glutamatergic neurons...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28018242/network-analysis-based-approach-for-exploring-the-potential-diagnostic-biomarkers-of-acute-myocardial-infarction
#4
Jiaqi Chen, Ling Yu, Siwei Zhang, Xia Chen
Acute myocardial infarction (AMI) is a severe cardiovascular disease that is a serious threat to human life. However, the specific diagnostic biomarkers have not been fully clarified and candidate regulatory targets for AMI have not been identified. In order to explore the potential diagnostic biomarkers and possible regulatory targets of AMI, we used a network analysis-based approach to analyze microarray expression profiling of peripheral blood in patients with AMI. The significant differentially-expressed genes (DEGs) were screened by Limma and constructed a gene function regulatory network (GO-Tree) to obtain the inherent affiliation of significant function terms...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27964744/differential-gene-and-protein-expression-of-chemokines-and-cytokines-in-synovial-fluid-of-patients-with-arthritis
#5
Anastasiya Muntyanu, Fatima Abji, Kun Liang, Remy A Pollock, Vinod Chandran, Dafna D Gladman
BACKGROUND: Psoriatic arthritis (PsA), an inflammatory musculoskeletal disease, develops in approximately 30% of patients with psoriasis. Previously, chemokine (C-X-C motif) ligand 10 (CXCL10) was identified as a predictive biomarker of PsA in patients with psoriasis and was reduced after development of PsA. The purpose of the present study was to explore messenger RNA (mRNA) and protein expression of CXCL10 and its receptor, chemokine (C-X-C motif) receptor 3 (CXCR3), in the joints of patients with PsA to gain insight into their role in the pathogenesis of the disease...
December 13, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27941786/transcriptional-programs-that-control-expression-of-the-autoimmune-regulator-gene-aire
#6
Yonatan Herzig, Shir Nevo, Chamutal Bornstein, Miriam R Brezis, Sharon Ben-Hur, Aya Shkedy, Michal Eisenberg-Bord, Ben Levi, Michael Delacher, Yael Goldfarb, Eyal David, Leehee Weinberger, Sergey Viukov, Shifra Ben-Dor, Matthieu Giraud, Jacob H Hanna, Achim Breiling, Frank Lyko, Ido Amit, Markus Feuerer, Jakub Abramson
Aire is a transcriptional regulator that induces promiscuous expression of thousands of genes encoding tissue-restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs). While the target genes of Aire are well characterized, the transcriptional programs that regulate its own expression have remained elusive. Here we comprehensively analyzed both cis-acting and trans-acting regulatory mechanisms and found that the Aire locus was insulated by the global chromatin organizer CTCF and was hypermethylated in cells and tissues that did not express Aire...
February 2017: Nature Immunology
https://www.readbyqxmd.com/read/27833268/interaction-between-anxa1-and-gata-3-in-immunosuppression-of-cd4-t-cells
#7
Peng Huang, Yuxiang Zhou, Zan Liu, Pihong Zhang
Decreased Th1/Th2 ratio is one of the major characteristics of immunosuppression in sepsis. Both membrane adhesive protein Annexin-A1 (ANXA1) and transcription factor GATA-3 have been reported to play important roles in T cell differentiation. However, the relationship between ANXA1 and GATA-3 in Th1/Th2 shift is unknown. Our study investigated the interaction effects of ANXA1 and GATA-3 to influence T cell differentiation in CD4(+) T cells. We found that GATA-3 and ANXA1 were coexpressed on Th0/Th1/Th2 cytoplasm and nuclear...
2016: Mediators of Inflammation
https://www.readbyqxmd.com/read/27764137/role-of-teffector-memory-cells-tbx21-gene-expression-and-t-cell-homing-receptor-on-type-1-reaction-in-borderline-lepromatous-leprosy-patients
#8
Luciana Nahar Dos Santos, Pedro Henrique Lopes da Silva, Iris Maria Peixoto Alvim, José Augusto da Costa Nery, Flávio Alves Lara, Euzenir Nunes Sarno, Danuza Esquenazi
In spite of hyporesponsivity to Mycobacterium leprae, borderline lepromatous (BL) patients show clinical and immunological instability, and undergo frequent acute inflammatory episodes such as type 1 reaction (T1R), which may cause nerve damages. This work focused on the participation of T cell subsets from blood and skin at T1R onset. We observed a significantly increased ex vivo frequency of both effector and memory CD4+ and CD8+ T cells in T1R group. Besides, ex vivo frequency of T cell homing receptor, the Cutaneous Leukocyte-associated Antigen (CLA) was significantly increased in T cells from T1R patients...
2016: PloS One
https://www.readbyqxmd.com/read/27757299/intratumoral-expression-levels-of-pd-l1-gzma-and-hla-a-along-with-oligoclonal-t-cell-expansion-associate-with-response-to-nivolumab-in-metastatic-melanoma
#9
Hiroyuki Inoue, Jae-Hyun Park, Kazuma Kiyotani, Makda Zewde, Azusa Miyashita, Masatoshi Jinnin, Yukiko Kiniwa, Ryuhei Okuyama, Ryota Tanaka, Yasuhiro Fujisawa, Hiroshi Kato, Akimichi Morita, Jun Asai, Norito Katoh, Kenji Yokota, Masashi Akiyama, Hironobu Ihn, Satoshi Fukushima, Yusuke Nakamura
Immune checkpoint inhibitors blocking the interaction between programmed death-1 (PD-1) and PD-1 ligand-1 (PD-L1) are revolutionizing the cancer immunotherapies with durable clinical responses. Although high expression of PD-L1 in tumor tissues has been implicated to correlate with the better response to the anti-PD-1 therapies, this association has been controversial. In this study, to characterize immune microenvironment in tumors, we examined mRNA levels of immune-related genes and characterized T cell repertoire in the tumors of 13 melanoma patients before and after nivolumab treatment...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27576126/human-circulating-group-2-innate-lymphoid-cells-can-express-cd154-and-promote-ige-production
#10
Laura Maggi, Gianni Montaini, Alessio Mazzoni, Beatrice Rossettini, Manuela Capone, Maria Caterina Rossi, Veronica Santarlasci, Francesco Liotta, Oliviero Rossi, Oreste Gallo, Raffaele De Palma, Enrico Maggi, Lorenzo Cosmi, Sergio Romagnani, Francesco Annunziato
BACKGROUND: Protection against helminths consists of adaptive responses by TH2 cells and innate responses by group 2 innate lymphoid cells (ILC2s), with these latter being well characterized in mice but less so in human subjects. OBJECTIVE: We sought to characterize human circulating ILC2s and compare their functional profile with that of autologous TH2 cells. METHODS: Circulating ILC2s and TH2 cells were isolated by means of fluorescence-activated cell sorting and magnetic cell sorting and expanded in vitro...
July 27, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27530627/variations-in-t-cell-transcription-factor-gene-structure-and-expression-associated-with-the-two-disease-forms-of-sheep-paratuberculosis
#11
Louise Nicol, Hazel Wilkie, Anton Gossner, Craig Watkins, Robert Dalziel, John Hopkins
Two different forms of clinical paratuberculosis in sheep are recognised, related to the level of bacterial colonization. Paucibacillary lesions are largely composed of lymphocytes with few bacteria, and multibacillary pathology is characterized by heavily-infected macrophages. Analysis of cytokine transcripts has shown that inflammatory Th1/Th17 T cells are associated with development of paucibacillary pathology and Th2 cytokines are correlated with multibacillary disease. The master regulator T cell transcription factors TBX21, GATA3, RORC2 and RORA are critical for the development of these T cell subsets...
2016: Veterinary Research
https://www.readbyqxmd.com/read/27511303/molecular-immunology-profiles-of-monkeys-following-xenografting-with-the-islets-and-heart-of-%C3%AE-1-3-galactosyltransferase-knockout-pigs
#12
Sun A Ock, Jungkyu Lee, Keon Bong Oh, Seongsoo Hwang, Ik Jin Yun, Curie Ahn, Hyun Keun Chee, Hwajung Kim, Jae Berm Park, Sung Joo Kim, Youngim Kim, Gi-Sun Im, EungWoo Park
Effective immunosuppression strategies and genetically modified animals have been used to prevent hyperacute and acute xenograft rejection; however, the underlying mechanisms remain unknown. In this study, we evaluated the expression of a comprehensive set of immune system-related genes (89 genes, including five housekeeping genes) in the blood of cynomolgus monkeys (~5 yr old) used as graft recipients, before and after the xenografting of the islets and heart from single and double α-1,3-galactosyltransferase (GalT) knockout (KO) pigs (<6 weeks old)...
September 2016: Xenotransplantation
https://www.readbyqxmd.com/read/27501956/the-leishmanicidal-activity-of-oleuropein-is-selectively-regulated-through-inflammation-and-oxidative-stress-related-genes
#13
Ioannis D Kyriazis, Olga S Koutsoni, Nektarios Aligiannis, Kalliopi Karampetsou, Alexios-Leandros Skaltsounis, Eleni Dotsika
BACKGROUND: Much research effort has been focused on investigating new compounds derived from low-cost sources, such as natural products, for treating leishmaniasis. Oleuropein derived from numerous plants, particularly from the olive tree, Olea europaea L. (Oleaceae), is a biophenol with many biological activities. Our previous findings showed that oleuropein exhibits leishmanicidal effects against three Leishmania spp. in vitro, and minimizes the parasite burden in L. donovani-infected BALB/c mice...
2016: Parasites & Vectors
https://www.readbyqxmd.com/read/27386265/increased-expression-of-tbet-in-cd4-t-cells-from-clinically-isolated-syndrome-patients-at-high-risk-of-conversion-to-clinically-definite-ms
#14
Sharee A Basdeo, Siobhan Kelly, Karen O'Connell, Niall Tubridy, Christopher McGuigan, Jean M Fletcher
BACKGROUND: The ability to identify clinically isolated syndrome (CIS) patients at high risk of progression to clinically definite multiple sclerosis (CDMS) would be clinically beneficial. The initiation of T cell mediated autoimmune diseases such as multiple sclerosis (MS) requires the initial inappropriate activation and differentiation of auto-reactive CD4(+) T cells. The quiescence of naive T cells is actively maintained by molecules such as TOB1, which control the threshold of activation...
2016: SpringerPlus
https://www.readbyqxmd.com/read/27307212/ifnl3-4-genotype-is-associated-with-altered-immune-cell-populations-in-peripheral-blood-in-chronic-hepatitis-c-infection
#15
K S O'Connor, S A Read, M Wang, S Schibeci, M Eslam, A Ong, M D Weltman, M W Douglas, A Mazzola, A Craxì, S Petta, G J Stewart, C Liddle, J George, G Ahlenstiel, D R Booth
Single-nucleotide polymorphisms near the interferon lambda 3 (IFNL3) gene predict outcomes to infection and anti-viral treatment in hepatitis C virus (HCV) infection. To identify IFNL3 genotype effects on peripheral blood, we collected phenotype data on 400 patients with genotype 1 chronic hepatitis C (CHC). The IFNL3 responder genotype predicted significantly lower white blood cells (WBCs), as well as lower absolute numbers of monocytes, neutrophils and lymphocytes for both rs8099917 and rs12979860. We sought to define the WBC subsets driving this association using flow cytometry of 67 untreated CHC individuals...
September 2016: Genes and Immunity
https://www.readbyqxmd.com/read/27256343/pathways-and-gene-networks-mediating-the-regulatory-effects-of-cannabidiol-a-nonpsychoactive-cannabinoid-in-autoimmune-t-cells
#16
Ewa Kozela, Ana Juknat, Fuying Gao, Nathali Kaushansky, Giovanni Coppola, Zvi Vogel
BACKGROUND: Our previous studies showed that the non-psychoactive cannabinoid, cannabidiol (CBD), ameliorates the clinical symptoms in mouse myelin oligodendrocyte glycoprotein (MOG)35-55-induced experimental autoimmune encephalomyelitis model of multiple sclerosis (MS) as well as decreases the memory MOG35-55-specific T cell (TMOG) proliferation and cytokine secretion including IL-17, a key autoimmune factor. The mechanisms of these activities are currently poorly understood. METHODS: Herein, using microarray-based gene expression profiling, we describe gene networks and intracellular pathways involved in CBD-induced suppression of these activated memory TMOG cells...
2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27226296/transcriptional-regulator-bhlhe40-works-as-a-cofactor-of-t-bet-in-the-regulation-of-ifn-%C3%AE-production-in-inkt-cells
#17
Masatoshi Kanda, Hiroyuki Yamanaka, Satoshi Kojo, Yuu Usui, Hiroaki Honda, Yusuke Sotomaru, Michishige Harada, Masaru Taniguchi, Nao Suzuki, Tatsuya Atsumi, Haruka Wada, Muhammad Baghdadi, Ken-Ichiro Seino
Invariant natural killer T (iNKT) cells are a subset of innate-like T cells that act as important mediators of immune responses. In particular, iNKT cells have the ability to immediately produce large amounts of IFN-γ upon activation and thus initiate immune responses in various pathological conditions. However, molecular mechanisms that control IFN-γ production in iNKT cells are not fully understood. Here, we report that basic helix-loop-helix transcription factor family, member e40 (Bhlhe40), is an important regulator for IFN-γ production in iNKT cells...
14, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27183623/tbet-or-continued-ror%C3%AE-t-expression-is-not-required-for-th17-associated-immunopathology
#18
Verena Brucklacher-Waldert, Cristina Ferreira, Silvia Innocentin, Shraddha Kamdar, David R Withers, Marika C Kullberg, Marc Veldhoen
The discovery of Th17 cell plasticity, in which CD4(+) IL-17-producing Th17 cells give rise to IL-17/IFN-γ double-producing cells and Th1-like IFNγ(+) ex-Th17 lymphocytes, has raised questions regarding which of these cell types contribute to immunopathology during inflammatory diseases. In this study, we show using Helicobacter hepaticus-induced intestinal inflammation that IL-17A(Cre)- or Rag1(Cre)-mediated deletion of Tbx21 has no effect on the generation of IL-17/IFN-γ double-producing cells, but leads to a marked absence of Th1-like IFNγ(+) ex-Th17 cells...
June 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27165068/comparison-of-the-expression-profiles-of-immune-response-gene-mrna-in-umbilical-and-venous-blood-of-newborns-of-the-first-day-of-life
#19
COMPARATIVE STUDY
O S Nepsha, I V Nikitina, A E Donnikov, A A Bystritsky, S M Mullabaeva, S V Pavlovich, N V Aleksandrova
The expression of immune response gene mRNA in the umbilical and venous blood were compared in newborns of the first day of life with and without signs of infection. The expression of il1b, il6, il8, il10, il12a, il15, il18, tnfa, tgfb1, tbx21, gata3, foxp3, rorc2, cd45, cd68, cd69, tlr2, tlr4, tlr9, and mmp8 mRNA was evaluated in umbilical and venous blood cells of newborns by reverse transcription real time PCR. In full-term newborns without signs of infection, the expression of il8, tlr2, tlr4, and mmp8 in venous blood was higher than in umbilical blood, while in preterm newborns, the levels of mmp8 transcript were elevated while the levels of tlr9, cd45, and gata3 were reduced...
April 2016: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27125523/genetic-association-of-ankylosing-spondylitis-with-tbx21-influences-t-bet-and-pro-inflammatory-cytokine-expression-in-humans-and-skg-mice-as-a-model-of-spondyloarthritis
#20
Max C Lau, Patricia Keith, Mary-Ellen Costello, Linda A Bradbury, Kelly A Hollis, Ranjeny Thomas, Gethin P Thomas, Matthew A Brown, Tony J Kenna
OBJECTIVES: Ankylosing spondylitis (AS) is a highly heritable immune-mediated arthropathy. Inflammation in AS is poorly understood. TBX21 encodes T-bet, a transcription factor, lying within a locus with genome-wide significant association with AS. T-bet is implicated in innate and adaptive immunity. However, the role of T-bet in AS pathogenesis is unclear. METHODS: We assessed the importance of T-bet in disease development and progression in peripheral blood mononuclear cells from 172 AS cases and 83 healthy controls carrying either risk or protective alleles of the peak AS-associated TBX21 single nucleotide polymorphism...
January 2017: Annals of the Rheumatic Diseases
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