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immune regulatory function

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https://www.readbyqxmd.com/read/29161273/enrichment-of-colorectal-cancer-associations-in-functional-regions-insight-for-using-epigenomics-data-in-the-analysis-of-whole-genome-sequence-imputed-gwas-data
#1
Stephanie A Bien, Paul L Auer, Tabitha A Harrison, Conghui Qu, Charles M Connolly, Peyton G Greenside, Sai Chen, Sonja I Berndt, Stéphane Bézieau, Hyun M Kang, Jeroen Huyghe, Hermann Brenner, Graham Casey, Andrew T Chan, John L Hopper, Barbara L Banbury, Jenny Chang-Claude, Stephen J Chanock, Robert W Haile, Michael Hoffmeister, Christian Fuchsberger, Mark A Jenkins, Suzanne M Leal, Mathieu Lemire, Polly A Newcomb, Steven Gallinger, John D Potter, Robert E Schoen, Martha L Slattery, Joshua D Smith, Loic Le Marchand, Emily White, Brent W Zanke, Goncalo R Abeçasis, Christopher S Carlson, Ulrike Peters, Deborah A Nickerson, Anshul Kundaje, Li Hsu
BACKGROUND: The evaluation of less frequent genetic variants and their effect on complex disease pose new challenges for genomic research. To investigate whether epigenetic data can be used to inform aggregate rare-variant association methods (RVAM), we assessed whether variants more significantly associated with colorectal cancer (CRC) were preferentially located in non-coding regulatory regions, and whether enrichment was specific to colorectal tissues. METHODS: Active regulatory elements (ARE) were mapped using data from 127 tissues and cell-types from NIH Roadmap Epigenomics and Encyclopedia of DNA Elements (ENCODE) projects...
2017: PloS One
https://www.readbyqxmd.com/read/29159704/neuroimmune-regulation-of-jc-virus-by-intracellular-and-extracellular-agnoprotein
#2
Michael Craigie, Stephanie Cicalese, Ilker Kudret Sariyer
JC virus (JCV) is a human polyomavirus and the etiologic agent of the demyelinating disease progressive multifocal leukoencephalopathy (PML). PML is observed in patients with underlying immunocompromising conditions, suggesting that neuro-immune interactions between peripheral immune cells and neuro-glia play an important role in controlling viral reactivation in the brain. There is little known about the immunobiology of JCV reactivation in glial cells and the role of immune, glial, and viral players in this regulation...
November 20, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/29159195/cd4-t-cells-from-multiple-sclerosis-patients-respond-to-a-commensal-derived-antigen
#3
Joseph N Burgess, Anudeep B Pant, Lloyd H Kasper, Sara Colpitts Brass
Multiple sclerosis, an immune-mediated disease of the central nervous system, is characterized by the impaired function of regulatory cells that fail to suppress self-reactive effector cells. We have previously found that polysaccharide A, a capsular antigen derived from the human gut commensal Bacteroides fragilis, can induce a population of regulatory T cells. Herein, we demonstrate that naïve T cells isolated from patients with multiple sclerosis have the capacity to acquire regulatory characteristics when stimulated in vitro with polysaccharide A...
November 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/29158586/insights-into-gene-expression-profiles-induced-by-socs3-depletion-in-keratinocytes
#4
Archana Bajpai, Takashi Ishii, Kosuke Miyauchi, Vipul Gupta, Yuka Nishio-Masaike, Yuki Shimizu-Yoshida, Masato Kubo, Hiroaki Kitano
Specific deletion of suppressor of cytokine signaling 3 (Socs3) in keratinocytes can cause severe skin inflammation with infiltration of immune cells. The molecular mechanisms and key regulatory pathways involved in these processes remain elusive. To investigate the role of Socs3 in keratinocytes, we generated and analyzed global RNA-Seq profiles from Socs3 conditional knockout (cKO) mice of two different ages (2 and 10 weeks). Over 400 genes were significantly regulated at both time points. Samples from 2-week-old mice exhibited down-regulation of genes involved in keratin-related functions and up-regulation of genes involved in lipid metabolism...
November 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29158334/global-transcriptome-sequencing-reveals-molecular-profiles-of-summer-diapause-induction-stage-of-onion-maggot-delia-antiqua-diptera-anthomyiidae
#5
Shuang Ren, You-Jin Hao, Bin Chen, You-Ping Yin
The onion maggot, Delia antiqua, is a worldwide subterranean pest and can enter diapause during summer and winter seasons. The molecular regulation of the ontogenesis transition remains largely unknown. Here we used high-throughput RNA-Seq to identify candidate genes and processes linked to summer diapause induction by comparing the transcriptome differences between the most sensitive larval developmental stage of summer-diapause (SD) and non-diapause (ND). Nine pair-wise comparisons were performed and significantly differentially regulated transcripts were identified...
November 20, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29157295/single-cell-multiplexed-cytokine-profiling-of-cd19-car-t-cells-reveals-a-diverse-landscape-of-polyfunctional-antigen-specific-response
#6
Qiong Xue, Emily Bettini, Patrick Paczkowski, Colin Ng, Alaina Kaiser, Timothy McConnell, Olja Kodrasi, Máire F Quigley, James Heath, Rong Fan, Sean Mackay, Mark E Dudley, Sadik H Kassim, Jing Zhou
BACKGROUND: It remains challenging to characterize the functional attributes of chimeric antigen receptor (CAR)-engineered T cell product targeting CD19 related to potency and immunotoxicity ex vivo, despite promising in vivo efficacy in patients with B cell malignancies. METHODS: We employed a single-cell, 16-plex cytokine microfluidics device and new analysis techniques to evaluate the functional profile of CD19 CAR-T cells upon antigen-specific stimulation. CAR-T cells were manufactured from human PBMCs transfected with the lentivirus encoding the CD19-BB-z transgene and expanded with anti-CD3/anti-CD28 coated beads...
November 21, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29155454/harnessing-the-power-of-regulatory-t-cells-to-control-autoimmune-diabetes-overview-and-perspective
#7
REVIEW
Hua Yu, Ricardo Paiva, Richard A Flavell
Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease resulting in islet β-cell destruction, hypoinsulinemia, and severely altered glucose homeostasis. Although the mechanisms that initiate T1D still remain elusive, a breakdown of immune tolerance between effector T cells (Teff) and regulatory T cells (Treg) is considered to be the crucial component leading to autoimmunity. As such, strategies have been developed to boost the number and/or function of Treg in the hope of specifically hampering the pathogenic Teff activity...
November 20, 2017: Immunology
https://www.readbyqxmd.com/read/29154757/macrophage-polarization-and-meta-inflammation
#8
REVIEW
Chuan Li, Maria M Xu, Kepeng Wang, Adam J Adler, Anthony T Vella, Beiyan Zhou
Chronic overnutrition and obesity induces low-grade inflammation throughout the body. Termed "meta-inflammation," this chronic state of inflammation is mediated by macrophages located within the colon, liver, muscle, and adipose tissue. A sentinel orchestrator of immune activity and homeostasis, macrophages adopt variable states of activation as a function of time and environmental cues. Meta-inflammation phenotypically skews these polarization states and has been linked to numerous metabolic disorders. The past decade has revealed several key regulators of macrophage polarization, including the signal transducer and activator of transcription family, the peroxisome proliferator-activated receptor gamma, the CCAAT-enhancer-binding proteins (C/EBP) family, and the interferon regulatory factors...
November 3, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29154208/characteristics-of-nk-cells-from-leukemic-microenvironment-in-mll-af9-induced-acute-myeloid-leukemia
#9
Feifei Yang, Rong Wang, Wenli Feng, Chong Chen, Xiao Yang, Lina Wang, Yuting Hu, Qian Ren, Guoguang Zheng
NK cells are indispensable components of tissue microenvironment and play vital in both innate and adaptive immunity. The activation and function of NK cells are affected by tumor microenvironments. NK cells are also important players in leukemic microenvironment. However, their characteristics in leukemic microenvironment, including maturation status, phenotype, subpopulations and functional roles especially immunoregulatory potential, have not been well established. Here, we studied these characteristics of NK cells in MLL-AF9 induced mouse acute myeloid leukemia (AML) model...
November 16, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29153034/advances-in-maldi-mass-spectrometry-within-drug-discovery
#10
Dale S Cornett, Michael D Scholle
Inhibition of NK and effector T-cell functions and activation of regulatory cell populations are the main immunosuppressive effects of indoleamine-2,3-dioxygenase1 (IDO1). By converting tryptophan (Trp) into kynurenine (Kyn), IDO1 is involved in the immune response homeostasis, and its dysregulated expression is described in immune-related pathologies, as tumors that hijack it to evade immune destruction. Thereby, IDO1 inhibitors are being developed to stimulate antitumor immune responses. Existing and standard quantitation methods of IDO1 substrate and metabolite(s) are based on the total level of Trp and its metabolites determined by liquid chromatography tandem mass spectrometry analysis in human plasma, cerebrospinal fluid, and brain...
December 2017: SLAS Discovery
https://www.readbyqxmd.com/read/29152379/interplay-of-neuronal-and-non-neuronal-genes-regulates-intestinal-daf-16-mediated-immune-response-during-fusarium-infection-of-caenorhabditis-elegans
#11
Papri Nag, Pooja Rani Aggarwal, Sudip Ghosh, Kanika Narula, Rajul Tayal, Nidhi Maheshwari, Niranjan Chakraborty, Subhra Chakraborty
Although precisely controlled innate immune response is governed by conserved cellular events in phylogenetically diverse hosts, the underlying molecular mechanisms by which this process is regulated against a multi-host pathogen remain unknown. Fusarium oxysporum is a model multi-host pathogen, known to be associated with neuronal stress in humans and vascular wilt in plants. The interaction between innate immune and neuronal pathways is the basis of many diverse biological responses. How these processes are coordinated in response to fungal disease is not well understood...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/29151862/profiling-the-immunome-of-little-brown-myotis-provides-a-yardstick-for-measuring-the-genetic-response-to-white-nose-syndrome
#12
Michael E Donaldson, Christina M Davy, Craig K R Willis, Scott McBurney, Allysia Park, Christopher J Kyle
White-nose syndrome (WNS) has devastated populations of hibernating bats in eastern North America, leading to emergency conservation listings for several species including the previously ubiquitous little brown myotis (Myotis lucifugus). However, some bat populations near the epicenter of the WNS panzootic appear to be stabilizing after initial precipitous declines, which could reflect a selective immunogenetic sweep. To investigate the hypothesis that WNS exerts significant selection on the immunome of affected bat populations, we developed a novel, high-throughput sequence capture assay targeting 138 adaptive, intrinsic, and innate immunity genes of putative adaptive significance, as well as their respective regulatory regions (~370 kbp of genomic sequence/individual)...
December 2017: Evolutionary Applications
https://www.readbyqxmd.com/read/29151021/regulatory-t-cells-induced-by-b-cells-a-novel-subpopulation-of-regulatory-t-cells
#13
REVIEW
Chien-Hui Chien, Bor-Luen Chiang
Regulatory T cells play a crucial role in the homeostasis of the immune response. In addition to CD4(+)Foxp3(+) regulatory T cells, several subsets of Foxp3(-) regulatory T cells, such as T helper 3 (Th3) cells and type 1 regulatory T (Tr1) cells, have been described in mice and human. Accumulating evidence shows that naïve B cells contribute to tolerance and are able to promote regulatory T cell differentiation. Naïve B cells can convert CD4(+)CD25(-) T cells into CD25(+)Foxp3(-) regulatory T cells, named Treg-of-B cells by our group...
November 18, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/29150659/ectopic-foxp3-expression-preserves-primitive-features-of-human-hematopoietic-stem-cells-while-impairing-functional-t-cell-differentiation
#14
F R Santoni de Sio, L Passerini, M M Valente, F Russo, L Naldini, M G Roncarolo, R Bacchetta
FOXP3 is the transcription factor ruling regulatory T cell function and maintenance of peripheral immune tolerance, and mutations in its coding gene causes IPEX autoimmune syndrome. FOXP3 is also a cell-cycle inhibitor and onco-suppressor in different cell types. In this work, we investigate the effect of ectopic FOXP3 expression on HSC differentiation and we challenged this approach as a possible HSC-based gene therapy for IPEX. FOXP3-expressing HSC showed reduced proliferation ability and increased maintenance of primitive markers in vitro in both liquid and OP9-ΔL1 co-cultures...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29150651/comprehensive-functional-enrichment-analysis-of-male-infertility
#15
Seyed Morteza Razavi, Marjan Sabbaghian, Mahdi Jalili, Adeleh Divsalar, Olaf Wolkenhauer, Ali Salehzadeh-Yazdi
Spermatogenesis is a multifactorial process that forms differentiated sperm cells in a complex microenvironment. This process involves the genome, epigenome, transcriptome, and proteome to ensure the stability of the spermatogonia and supporting cells. The identification of signaling pathways linked to infertility has been hampered by the inherent complexity and multifactorial aspects of spermatogenesis. Systems biology is a promising approach to unveil underlying signaling pathways and genes and identify putative biomarkers...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29149782/frequency-of-circulatory-regulatory-immune-cells-in-iranian-patients-with-type-1-diabetes
#16
Tahereh Khamehchian, Eqlim Nemati, Marziyeh Jazayeri, Shirin Azimi, Hassan Nikoueinejad, Hossein Akbari, Behnaz Irandoust
Type 1 diabetes (T1D) is the result of the autoimmune destruction of insulin-producing beta cells. Regulatory T cells (Tregs) and plasmacytoid dendritic cells (PDCs) act as mediators of peripheral tolerance. We investigated the possible alterations of such cells in peripheral blood of patients with T1D compared to normal individuals. This comparison may lead to a better understanding of the immunopathogenesis processes involved in T1D. 92 participants, including 49 patients with T1D and 43 healthy controls were studied...
October 2017: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/29149404/the-translational-controlled-tumour-protein-tctp-biological-functions-and-regulation
#17
Ulrich-Axel Bommer
The Translational Controlled Tumour Protein TCTP (gene symbol TPT1, also called P21, P23, Q23, fortilin or histamine-releasing factor, HRF) is a highly conserved protein present in essentially all eukaryotic organisms and involved in many fundamental cell biological and disease processes. It was first discovered about 35 years ago, and it took an extended period of time for its multiple functions to be revealed, and even today we do not yet fully understand all the details. Having witnessed most of this history, in this chapter, I give a brief overview and review the current knowledge on the structure, biological functions, disease involvements and cellular regulation of this protein...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/29147615/tumor-associated-neutrophils-induce-apoptosis-of-non-activated-cd8-t-cells-in-a-tnf%C3%AE-and-no-dependent-mechanism-promoting-a-tumor-supportive-environment
#18
Janna Michaeli, Merav E Shaul, Inbal Mishalian, Avi-Hai Hovav, Liran Levy, Lidia Zolotriov, Zvi Granot, Zvi G Fridlender
The role of neutrophils in tumor progression has become in recent years a subject of growing interest. Tumor-associated neutrophils (TANs), which constitute an important portion of the tumor microenvironment, promote immunosuppression in advanced tumors by modulating the proliferation, activation and recruitment of a variety of immune cell types. Studies which investigated the consequences of manipulating TAN polarization suggest that the impact of these neutrophils on tumor progression is considerably mediated by and dependent on the presence of CD8 T-cells...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147602/gdnf-secreted-by-nerves-enhances-pd-l1-expression-via-jak2-stat1-signaling-activation-in-hnscc
#19
Chengzhong Lin, Wei Cao, Zhenhu Ren, Yu Tang, Chunye Zhang, Rong Yang, Yiming Chen, Zheqi Liu, Canbang Peng, Lizhen Wang, Xu Wang, Tong Ji
Programmed death ligand 1 (PD-L1) functions as a key immune inhibitory factor by binding with its receptor, programmed death 1 (PD-1), to induce immune cell dysfunction and escape of the immune system. However, the mechanisms of PD-L1 expression under growth factor stimulation are not well characterized. Here, we demonstrate a novel role for glial cell line-derived neurotrophic factor (GDNF) in upregulating PD-L1 expression in head and neck squamous cell carcinoma (HNSCC). The expression and correlation of PD-L1, GDNF and perineural invasion (PNI) status were evaluated by bioinformatics analysis of TCGA database and IHC assays from 145 HNSCC patients...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147008/the-transcription-factor-batf3-inhibits-the-differentiation-of-regulatory-t-cells-in-the-periphery
#20
Wonyong Lee, Hyeong Su Kim, Soo Seok Hwang, Gap Ryol Lee
Naive CD4 T cells activated by antigen-presenting cells (APCs) undergo terminal differentiation in the periphery. Multiple mechanisms determine their fates, that is, whether they differentiate into conventional T (Tconv) cells or regulatory T (Treg) cells. The key event during Treg generation is expression of the transcription factor Foxp3, which is the lineage-determining regulator for Treg differentiation and function. Here we show that the transcription factor Batf3 acts as a fate-decision factor with respect to Tconv versus Tregs by restraining Treg differentiation...
November 17, 2017: Experimental & Molecular Medicine
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