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https://www.readbyqxmd.com/read/28097811/fc-silent-anti-cd154-domain-antibody-effectively-prevents-non-human-primate-renal-allograft-rejection
#1
Steven C Kim, Walter Wakwe, Laura B Higginbotham, David V Mathews, Cynthia P Breeden, Allison C Stephenson, Joe Jenkins, Elizabeth Strobert, Karen Price, Laura Price, Robert Kuhn, Haiqing Wang, Aaron Yamniuk, Suzanne Suchard, Alton B Farris, Thomas C Pearson, Christian P Larsen, Mandy L Ford, Anish Suri, Steven Nadler, Andrew B Adams
The advent of costimulation blockade provides the prospect for targeted therapy with improved graft survival in transplant patients. Perhaps the most effective costimulation blockade in experimental models is the use of reagents to block the CD40/CD154 pathway. Unfortunately, successful clinical translation of anti-CD154 therapy has not been achieved. In an attempt to develop an agent that is as effective as previous CD154 blocking antibodies but lacks the risk of thromboembolism, we evaluated the efficacy and safety of a novel anti-human CD154 domain antibody (dAb, BMS-986004)...
January 17, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28097735/autoimmune-enteropathy-and-hepatitis-in-pediatric-heart-transplant-recipient
#2
Kimberly Lewis, Ryan Butts, J Antonio Quiros, Michelle Hudspeth, Katherine Twombley, Andrew Savage, Sally Self, Ali Burnette, Shaoli Sun
AIE is a rare disorder in children that presents with severe diarrhea and malabsorption, caused by immune-mediated damage to intestinal mucosa. AIE is often associated with various syndromes of immunodeficiency including IPEX syndrome (immune dysregulation, polyendocrinopathy and enteropathy, X-linked). Dysfunctional T regulatory cells are the source of pathology in both IPEX syndrome and AIE as they are essential in maintaining tolerance to self-antigens and eliminating autoreactive B cells. This case report describes a 10-year-old cardiac transplant and total thymectomy patient on chronic immunosuppression with tacrolimus that presented with AIE and extraintestinal manifestations of cyclical hepatitis...
January 17, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28097234/kruppel-like-factor4-regulates-prdm1-expression-through-binding-to-an-autoimmune-risk-allele
#3
Su Hwa Jang, Helen Chen, Peter K Gregersen, Betty Diamond, Sun Jung Kim
A SNP identified as rs548234, which is found in PRDM1, the gene that encodes BLIMP1, is a risk allele associated with systemic lupus erythematosus (SLE). BLIMP1 expression was reported to be decreased in women with the PRDM1 rs548234 risk allele compared with women with the nonrisk allele in monocyte-derived DCs (MO-DCs). In this study, we demonstrate that BLIMP1 expression is regulated by the binding of Kruppel-like factor 4 (KLF4) to the risk SNP. KLF4 is highly expressed in MO-DCs but undetectable in B cells, consistent with the lack of altered expression of BLIMP1 in B cells from risk SNP carriers...
January 12, 2017: JCI Insight
https://www.readbyqxmd.com/read/28096300/enhanced-suppression-of-polyclonal-cd8-25-regulatory-t-cells-via-exosomal-arming-of-antigen-specific-peptide-mhc-complexes
#4
Chuanyong Mu, Xueshu Zhang, Lu Wang, Aizhang Xu, Khawaja Ashfaque Ahmed, Xueqin Pang, Rajni Chibbar, Andrew Freywald, Jianan Huang, Yehan Zhu, Jim Xiang
Compared with CD4(+)25(+) regulatory T cells (Tregs), the mechanisms for natural, polyclonal CD8(+)25(+) Treg immune suppression have been significantly less studied. We previously showed that polyclonal T cells can acquire antigen-specific targeting activity through arming with exosomal peptide-MHC (pMHC). In this study, we assessed the suppressive effect of CD8(+)25(+) Tregs or CD8(+)25(+) Tregs armed with ovalbumin (OVA)-specific exosomes on other immune cells and OVA-specific dendritic cell (DCOVA)-stimulated antitumor immunity...
January 17, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28095351/level-of-granzyme-b-positive-t-regulatory-cells-is-a-strong-predictor-biomarker-of-acute-graft-versus-host-disease-after-day-30-after-allo-hsct
#5
Mikhail Y Drokov, Julia O Davydova, Larisa A Kuzmina, Irina V Galtseva, Nikolay M Kapranov, Vera A Vasilyeva, Darya S Dubnyak, Olga M Koroleva, Ekaterina D Mikhalcova, Natalia N Popova, Elena N Parovichnikova, Valery G Savchenko
Acute Graft-versus-host-disease (aGVHD), the major complication and one of the main causes of poor outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Nowadays there are no widely accepted cell, plasma or another biomarker that can be used for aGVHD prediction. We hypothesized that a level of Granzyme B-positive T regulatory (GZMB-positive Treg) cells on day+30 after allo-HSCT could be the measure of immune response suppression and could predict aGVHD development after day +30. We applied a widespread and easy-to-perform method of multicolor flow cytometry to measure level of GZMB-positive Treg cells...
January 10, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28094813/a-methylome-wide-mqtl-analysis-reveals-associations-of-methylation-sites-with-gad1-and-hdac3-snps-and-a-general-psychiatric-risk-score
#6
D M Ciuculete, A E Boström, S Voisin, H Philipps, O E Titova, M Bandstein, L Nikontovic, M J Williams, J Mwinyi, H B Schiöth
Genome-wide association studies have identified a number of single-nucleotide polymorphisms (SNPs) that are associated with psychiatric diseases. Increasing body of evidence suggests a complex connection of SNPs and the transcriptional and epigenetic regulation of gene expression, which is poorly understood. In the current study, we investigated the interplay between genetic risk variants, shifts in methylation and mRNA levels in whole blood from 223 adolescents distinguished by a risk for developing psychiatric disorders...
January 17, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28094779/suppression-of-colitis-by-adoptive-transfer-of-helminth-antigen-treated-dendritic-cells-requires-interleukin-4-receptor-%C3%AE-signaling
#7
C E Matisz, B Faz-López, E Thomson, A Al Rajabi, F Lopes, L I Terrazas, A Wang, K A Sharkey, D M McKay
Infection with helminth parasites has been explored as a treatment for autoimmune and inflammatory diseases. As helminth antigens have potent immunomodulation properties capable of inducing regulatory programs in a variety of cell types, transferring cells treated with helminth antigens represents a novel extension to helminth therapy. Previous work determined that transfer of bone marrow-derived dendritic cells (DC) pulsed with a crude extract of the tapeworm Hymenolepis diminuta (HD) can suppress colitis in recipient mice...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28094574/inferring-a-role-for-methylation-of-intergenic-dna-in-the-regulation-of-genes-aberrantly-expressed-in-precursor-b-cell-acute-lymphoblastic-leukemia
#8
Md Almamun, Olha Kholod, Alexei J Stuckel, Benjamin T Levinson, Nathan T Johnson, Gerald L Arthur, J Wade Davis, Kristen H Taylor
A complete understanding of the mechanisms involved in the development of pre-B ALL is lacking. In this study, we integrated DNA methylation data and gene expression data to elucidate the impact of aberrant intergenic DNA methylation on gene expression in pre-B ALL. We found a subset of differentially methylated intergenic loci that were associated with altered gene expression in pre-B ALL patients. Notably, 84% of these regions were also bound by transcription factors (TF) known to play roles in differentiation and B-cell development in a lymphoblastoid cell line...
January 17, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28094101/retinoic-acid-and-immune-homeostasis-a-balancing-act
#9
REVIEW
Martje N Erkelens, Reina E Mebius
In the immune system, the vitamin A metabolite retinoic acid (RA) is known for its role in inducing gut-homing molecules in T and B cells, inducing regulatory T cells (Tregs), and promoting tolerance. However, it was suggested that RA can have a broad spectrum of effector functions depending on the local microenvironment. Under specific conditions, RA can also promote an inflammatory environment. We discuss the dual role of RA in immune responses and how this might be regulated. Furthermore, we focus on the role of RA in autoimmune diseases and whether RA might be used as a therapeutic agent...
January 13, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28093925/hypermethylation-of-antisense-long-noncoding-rnas-in-acute-lymphoblastic-leukemia
#10
Gerald Arthur, Md Almamun, Kristen Taylor
AIM: Long noncoding RNAs serve critical regulatory functions highly specific for a tissue and its developmental stage. Antisense long ncRNA (AS-lncRNA) methylation changes in acute lymphoblastic leukemia (ALL) versus normal pre-B-cell lymphoblasts were evaluated to identify potential differential methylation in this group of genes. MATERIALS & METHODS: The methylome of ALL and normal lymphoblasts was examined by the methylated CpG island recovery assay followed by NGS...
January 17, 2017: Epigenomics
https://www.readbyqxmd.com/read/28092672/bpgap1-spatially-integrates-jnk-erk-signaling-crosstalk-in-oncogenesis
#11
T Jiang, C Q Pan, B C Low
Simultaneous hyperactivation of stress-activated protein kinase/c-Jun N-terminal protein kinase (SAPK/JNK) and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) signaling cascades has been reported in carcinogenesis. However, how they are integrated to promote oncogenesis remains unknown. By analyzing breast invasive carcinoma database (The Cancer Genome Altas), we found that the mRNA expression levels of both JNK1 and ERK2 are positively correlated with the mRNA level of EEA1, an endosome associated protein, indicating the potential JNK/ERK crosstalk at endosome...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28088964/-the-influence-of-depression-degree-on-regulatory-t-cells-in-patients-with-non-m3-acute-myeloid-leukemia
#12
J Cao, B Yuan, P X Guo, H Q Zhu, Z Z Huang, Y He, Q Ding, Z Z Feng
Objective: To investigate the influence of depression levels on regulatory T cells (Tregs) in patients with non-M3 acute myeloid leukemia (AML). Methods: A total of 63 patients with primarily diagnostic non-M3 AML and 25 healthy controls were enrolled, and the levels of depression by using HADM score and the percentages of Tregs by flow cytometry were evaluated in pre-treatment and post-treatment, respectively. Results: After every course of chemotherapy, the percentages of Tregs of PBMNC in AML showed the higher level of (6...
December 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28088772/thrombospondin-immune-regulation-and-the-kidney
#13
Claudio Ponticelli, Hans-Joachim Anders
Most therapeutic attempts to prevent the progression of kidney diseases have been based on interventions to inhibit the production of transforming growth factor-β (TGF-β). Thrombospondins (TSPs) play an important role in activating TGF-β. In the healthy kidney, two TSPs are expressed, TSP1 and TSP2, which exert contrasting effects. While TSP1 is a major activator of TGF-β in renal cells and exerts pro-inflammatory effects both in vitro and in vivo, TSP2 lacks the ability for TGF-β activation but regulates matrix remodeling and inflammation in experimental kidney disease...
January 14, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28088385/flavonoid-derivative-fla-cn-inhibited-adipocyte-differentiation-via-activating-ampk-and-up-regulating-microrna-27-in-3t3-l1-cells
#14
Chun-Chun Gan, Tian-Wen Ni, Yang Yu, Nan Qin, Ying Chen, Mei-Na Jin, Hong-Quan Duan
Fla-CN (3-O-[(E)-4-(4-cyanophenyl)-2-oxobut-3-en-1-yl] kaempferol) is a semi-synthesized flavonoid derivative of tiliroside which exhibited anti-diabetic effect in vivo. Our previous study revealed the role of Fla-CN in anti-obesity and anti-diabetes in vivo, but the underlying mechanism remained to be addressed. The present study aimed to investigate the mechanism of anti-adipogenesis in vitro. Fla-CN markedly inhibited intracellular lipid accumulation in a dose-dependent manner, and the inhibitory effect was mainly limited to the early stage of adipocyte differentiation in vitro...
January 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28088132/expression-and-secretion-of-cyan-fluorescent-protein-cfp-in-b-subtilis-using-the-chitinase-promoter-from-bacillus-pumilus-sg2
#15
Abbas Shali, Garshasb Rigi, Majid Pornour, Gholamreza Ahmadian
Background: Improved cyan fluorescent protein (ICFP) is a monochromic, green fluorescent protein (GFP) derivative produced by Aequorea macrodactyla in a process similar to GFP. This protein has strong absorption spectra at wavelengths 426-446 nm. ICFP can be used in cell, organelle or intracellular protein labeling, investigating the protein-protein interactions as well as assessing the promoter activities. Methods: In our previous study, the promoters of two chitinases (ChiS and ChiL) from Bacillus pumilus SG2 were assessed in B...
15, 2017: Iranian Biomedical Journal
https://www.readbyqxmd.com/read/28087671/induction-and-differentiation-of-il-10-producing-regulatory-b-cells-from-healthy-blood-donors-and-rheumatoid-arthritis-patients
#16
Zsuzsanna Bankó, Judit Pozsgay, Dániel Szili, Mária Tóth, Tamás Gáti, György Nagy, Bernadette Rojkovich, Gabriella Sármay
The most important feature of B cells is the production of Abs upon activation; additionally, B cells produce pro- and anti-inflammatory cytokines in response to certain stimuli. IL-10-producing B cells represent a major subset of regulatory B cells (Bregs) that suppress autoimmune and inflammatory responses. B cells play a crucial role in the development and maintenance of the chronic inflammatory autoimmune disease rheumatoid arthritis (RA); however, controversial data are available on IL-10- producing Bregs in RA...
January 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28087520/atheroprotective-vaccination-with-mhc-ii-restricted-apob-peptides-induces-peritoneal-il-10-producing-cd4-t-cells
#17
Takayuki Kimura, Kevin Tse, Sara McArdle, Teresa Gerhardt, Jacqueline Miller, Zbigniew Mikulski, John Sidney, Alessandro Sette, Dennis Wolf, Klaus Ley
Although immunization with MHC class II-restricted ApoB peptides has been shown to be atheroprotective, the mechanism is unclear. Here, we investigated CD4(+) T cell populations in immunized atherosclerotic mice. Peptides (16-mers) from mouse ApoB, the core protein of low-density lipoprotein (LDL), were screened for binding to I-A(b) by computer prediction and confirmed by radiolabeled peptide competition. Three new peptides, P101 (FGKQGFFPDSVNKALY, 5.5 nM IC50), P102 (TLYALSHAVNSYFDVD, 6.8 nM), and P103 (LYYKEDKTSLSASAAS, 95 nM) were tested in an atherosclerosis model (Apoe(-/-) mice on western diet)...
January 13, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28081217/collective-genetic-interaction-effects-and-the-role-of-antigen-presenting-cells-in-autoimmune-diseases
#18
Hyung Jun Woo, Chenggang Yu, Jaques Reifman
Autoimmune diseases occur when immune cells fail to develop or lose their tolerance toward self and destroy body's own tissues. Both insufficient negative selection of self-reactive T cells and impaired development of regulatory T cells preventing effector cell activation are believed to contribute to autoimmunity. Genetic predispositions center around the major histocompatibility complex (MHC) class II loci involved in antigen presentation, the key determinant of CD4+ T cell activation. Recent studies suggested that variants in the MHC region also exhibit significant non-additive interaction effects...
2017: PloS One
https://www.readbyqxmd.com/read/28078793/insights-into-nuclear-dynamics-using-live-cell-imaging-approaches
#19
REVIEW
Rachel B Bigley, Alexander Y Payumo, Jeffrey M Alexander, Guo N Huang
The nucleus contains the genetic blueprint of the cell and myriad interactions within this subcellular structure are required for gene regulation. In the current scientific era, characterization of these gene regulatory networks through biochemical techniques coupled with systems-wide 'omic' approaches has become commonplace. However, these strategies are limited because they represent a mere snapshot of the cellular state. To obtain a holistic understanding of nuclear dynamics, relevant molecules must be studied in their native contexts in living systems...
January 12, 2017: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
https://www.readbyqxmd.com/read/28077791/carcinoma-risk-variant-of-ebna1-deregulates-epstein-barr-virus-episomal-latency
#20
Jayaraju Dheekollu, Kimberly Malecka, Andreas Wiedmer, Henri-Jacques Delecluse, Alan Ks Chiang, Dario C Altieri, Troy E Messick, Paul M Lieberman
Epstein-Barr Virus (EBV) latent infection is a causative co-factor for endemic Nasopharyngeal Carcinoma (NPC). NPC-associated variants have been identified in EBV-encoded nuclear antigen EBNA1. Here, we solve the X-ray crystal structure of an NPC-derived EBNA1 DNA binding domain (DBD) and show that variant amino acids are found on the surface away from the DNA binding interface. We show that NPC-derived EBNA1 is compromised for DNA replication and episome maintenance functions. Recombinant virus containing the NPC EBNA1 DBD are impaired in their ability to immortalize primary B-lymphocytes and suppress lytic transcription during early stages of B-cell infection...
January 6, 2017: Oncotarget
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