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Tregs OR regulatory T cells

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https://www.readbyqxmd.com/read/28339459/functional-classification-of-dna-variants-by-hybrid-minigenes-identification-of-30-spliceogenic-variants-of-brca2-exons-17-and-18
#1
Eugenia Fraile-Bethencourt, Beatriz Díez-Gómez, Valeria Velásquez-Zapata, Alberto Acedo, David J Sanz, Eladio A Velasco
Mutation screening of the breast cancer genes BRCA1 and BRCA2 identifies a large fraction of variants of uncertain clinical significance (VUS) whose functional and clinical interpretations pose a challenge for genomic medicine. Likewise, an increasing amount of evidence indicates that genetic variants can have deleterious effects on pre-mRNA splicing. Our goal was to investigate the impact on splicing of a set of reported variants of BRCA2 exons 17 and 18 to assess their role in hereditary breast cancer and to identify critical regulatory elements that may constitute hotspots for spliceogenic variants...
March 24, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28335009/open-chromatin-profiling-of-human-postmortem-brain-infers-functional-roles-for-non-coding-schizophrenia-loci
#2
John F Fullard, Claudia Giambartolomei, Mads E Hauberg, Ke Xu, Georgios Voloudakis, Zhiping Shao, Christopher Bare, Joel T Dudley, Manuel Mattheisen, Nikolaos K Robakis, Vahram Haroutunian, Panos Roussos
Open chromatin provides access to DNA binding proteins for the correct spatiotemporal regulation of gene expression. Mapping chromatin accessibility has been widely used to identify the location of cis regulatory elements (CREs) including promoters and enhancers. CREs show tissue- and cell-type specificity and disease-associated variants are often enriched for CREs in the tissues and cells that pertain to a given disease. To better understand the role of CREs in neuropsychiatric disorders we applied the Assay for Transposase Accessible Chromatin followed by sequencing (ATAC-seq) to neuronal and non-neuronal nuclei isolated from frozen postmortem human brain by fluorescence-activated nuclear sorting (FANS)...
March 14, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334900/cdk12-regulates-alternative-last-exon-mrna-splicing-and-promotes-breast-cancer-cell-invasion
#3
Jerry F Tien, Alborz Mazloomian, S-W Grace Cheng, Christopher S Hughes, Christalle C T Chow, Leanna T Canapi, Arusha Oloumi, Genny Trigo-Gonzalez, Ali Bashashati, James Xu, Vicky C-D Chang, Sohrab P Shah, Samuel Aparicio, Gregg B Morin
CDK12 (cyclin-dependent kinase 12) is a regulatory kinase with evolutionarily conserved roles in modulating transcription elongation. Recent tumor genome studies of breast and ovarian cancers highlighted recurrent CDK12 mutations, which have been shown to disrupt DNA repair in cell-based assays. In breast cancers, CDK12 is also frequently co-amplified with the HER2 (ERBB2) oncogene. The mechanisms underlying functions of CDK12 in general and in cancer remain poorly defined. Based on global analysis of mRNA transcripts in normal and breast cancer cell lines with and without CDK12 amplification, we demonstrate that CDK12 primarily regulates alternative last exon (ALE) splicing, a specialized subtype of alternative mRNA splicing, that is both gene- and cell type-specific...
March 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334751/atp13a2-park9-regulates-endo-lysosomal-cargo-sorting-and-proteostasis-through-a-novel-pi-3-5-p2-mediated-scaffolding-function
#4
S Demirsoy, S Martin, S Motamedi, S van Veen, T Holemans, C Van den Haute, A Jordanova, V Baekelandt, P Vangheluwe, P Agostinis
ATP13A2 (also called PARK9), is a transmembrane endo-/lysosomal-associated P5 type transport ATPase. Loss-of-function mutations in ATP13A2 result in the Kufor-Rakeb Syndrome (KRS), a form of autosomal Parkinson's disease (PD). In spite of a growing interest in ATP13A2, very little is known about its physiological role in stressed cells. Recent studies suggest that the N-terminal domain of ATP13A2 may hold key regulatory functions, but their nature remains incompletely understood. To this end, we generated a set of melanoma and neuroblastoma cell lines stably overexpressing wild-type (WT), catalytically inactive (D508N) and N-terminal mutants, or shRNA against ATP13A2...
February 22, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28333899/-stem-progenitor-cells-in-diseases-of-the-respiratory-tract
#5
EDITORIAL
Tadeusz Płusa
Stem cells (SCs - stem cells) are characterized by plasticity and the ability to differentiate into other cell types. They are obtained from bone marrow, peripheral blood and cord blood. Mesenchymal stem cells (MSCs) shows a broad immunomodulating, increases the number of regulatory T cells (Treg), modifies the activity of T cells, dendritic cells and NK (natural killer). Direct impact on reducing the release of proinflammatory cytokines and increased release of proinflammatory cytokines. Within the respiratory tract has a number of resident stem and progenitor cells referred to as L-MSCs (lung mesenchymal stem cells) whose presence was confirmed by markers as defined in the trachea, epithelial cells and alveolar...
March 21, 2017: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/28333145/the-cryo-thermal-therapy-eradicated-melanoma-in-mice-by-eliciting-cd4-t-cell-mediated-antitumor-memory-immune-response
#6
Kun He, Ping Liu, Lisa X Xu
Tumor metastasis is a major concern in tumor therapy. In our previous studies, a novel tumor therapeutic modality of the cryo-thermal therapy has been presented, highlighting its effect on the suppression of distal metastasis and leading to long-term survival in 4T1 murine mammary carcinoma model. To demonstrate the therapeutic efficacy in other aggressive tumor models and further investigate the mechanism of long-term survival induced, in this study, spontaneous metastatic murine B16F10 melanoma model was used...
March 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28332605/janus-faced-acrolein-prevents-allergy-but-accelerates-tumor-growth-by-promoting-immunoregulatory-foxp3-cells-mouse-model-for-passive-respiratory-exposure
#7
Franziska Roth-Walter, Cornelia Bergmayr, Sarah Meitz, Stefan Buchleitner, Caroline Stremnitzer, Judit Fazekas, Anna Moskovskich, Mario A Müller, Georg A Roth, Krisztina Manzano-Szalai, Zdenek Dvorak, Alina Neunkirchner, Erika Jensen-Jarolim
Acrolein, a highly reactive unsaturated aldehyde, is generated in large amounts during smoking and is best known for its genotoxic capacity. Here, we aimed to assess whether acrolein at concentrations relevant for smokers may also exert immunomodulatory effects that could be relevant in allergy or cancer. In a BALB/c allergy model repeated nasal exposure to acrolein abrogated allergen-specific antibody and cytokine formation, and led to a relative accumulation of regulatory T cells in the lungs. Only the acrolein-treated mice were protected from bronchial hyperreactivity as well as from anaphylactic reactions upon challenge with the specific allergen...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28332566/a-conformational-change-within-the-wave2-complex-regulates-its-degradation-following-cellular-activation
#8
Noah Joseph, Guy Biber, Sophia Fried, Barak Reicher, Omer Levy, Batel Sabag, Elad Noy, Mira Barda-Saad
WASp family Verprolin-homologous protein-2 (WAVE2), a member of the Wiskott-Aldrich syndrome protein (WASp) family of actin nucleation promoting factors, is a central regulator of actin cytoskeleton polymerization and dynamics. Multiple signaling pathways operate via WAVE2 to promote the actin-nucleating activity of the actin-related protein 2/3 (Arp2/3) complex. WAVE2 exists as a part of a pentameric protein complex known as the WAVE regulatory complex (WRC), which is unstable in the absence of its individual proteins...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28332200/immunoregulation-of-inflammatory-and-inhibitory-cytokines-by-vitamin-d3-in-patients-with-inflammatory-bowel-diseases-ibd
#9
REVIEW
Hussaini Mohammed Alhassan, Abbas Mirshafiey, Homayoun Vahedi, Gholamreza Hemmasi, Ateke Moussavi Nasl Khameneh, Karim Parastouei, Ali Akbar Saboor-Yaraghi
Inflammatory bowel disease (IBD) is a group of idiopathic, chronic and relapsing inflammatory conditions of the gastrointestinal tract, caused by an aberrant and exaggerated immunological response in the gut. Supplementation of Vitamin D3 in IBD patients exerts both direct and indirect regulatory roles on the naïve T-cells, thereby maintaining a balance between inflammatory and inhibitory cytokines. The direct actions of Vitamin D3 on naïve T-cells result in the proliferation of more regulatory T-cells and inhibitory cytokines such as IL-4, IL-10, and IL-5...
March 22, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28330901/azacitidine-mitigates-graft-versus-host-disease-via-differential-effects-on-the-proliferation-of-t-effectors-and-natural-regulatory-t-cells-in-vivo
#10
Matthew L Cooper, Jaebok Choi, Darja Karpova, Kiran Vij, Julie Ritchey, Mark A Schroeder, John F DiPersio
Azacitidine (AzaC) mitigates graft-versus-host disease (GvHD) in both murine preclinical transplant models and in human clinical trials while maintaining a robust graft-versus-leukemia effect. Previous studies have failed to investigate the role of natural regulatory T cells (nTregs) on the mitigation of GvHD by AzaC, instead focusing on the generation of suppressive Tregs (CD4(+)CD25(+)FOXP3(+)) through the in vivo conversion of alloreactive donor T effectors (Teffs; CD4(+)CD25(-)FOXP3(-)) and the direct antiproliferative effects of AzaC on allogeneic T cells...
March 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28330473/dynamic-and-specific-immune-responses-against-multiple-tumor-antigens-were-elicited-in-patients-with-hepatocellular-carcinoma-after-cell-based-immunotherapy
#11
Yanyan Han, Yeting Wu, Chou Yang, Jing Huang, Yabing Guo, Li Liu, Ping Chen, Dongyun Wu, Junyun Liu, Jin Li, Xiangjun Zhou, Jinlin Hou
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers in China and frequently occurs with chronic hepatitis B virus infection. To investigate whether cell-based cancer immunotherapy induces tumor specific immune responses in patients with HCC and provides clinical benefits, as well as to elucidate the most immunogenic tumor associated antigens (TAAs), multiple antigen stimulating cellular therapy (MASCT) was applied in addition to standard of care. METHODS: Mature dendritic cells (DCs) and activated T cells prepared for MASCT were generated from autologous peripheral blood mononuclear cells (PBMCs)...
March 22, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28329703/successful-and-maladaptive-t-cell-aging
#12
REVIEW
Jörg J Goronzy, Cornelia M Weyand
Throughout life, the T cell system adapts to shifting resources and demands, resulting in a fundamentally restructured immune system in older individuals. Here we review the cellular and molecular features of an aged immune system and discuss the trade-offs inherent to these adaptive mechanisms. Processes include homeostatic proliferation that maintains compartment size at the expense of partial loss in stemness and incomplete differentiation and the activation of negative regulatory programs, which constrain effector T cell expansion and prevent increasing oligoclonality but also interfere with memory cell generation...
March 21, 2017: Immunity
https://www.readbyqxmd.com/read/28329691/myocardial-infarction-primes-autoreactive-t-cells-through-activation-of-dendritic-cells
#13
Katrien Van der Borght, Charlotte L Scott, Veronika Nindl, Ann Bouché, Liesbet Martens, Dorine Sichien, Justine Van Moorleghem, Manon Vanheerswynghels, Sofie De Prijck, Yvan Saeys, Burkhard Ludewig, Thierry Gillebert, Martin Guilliams, Peter Carmeliet, Bart N Lambrecht
Peripheral tolerance is crucial for avoiding activation of self-reactive T cells to tissue-restricted antigens. Sterile tissue injury can break peripheral tolerance, but it is unclear how autoreactive T cells get activated in response to self. An example of a sterile injury is myocardial infarction (MI). We hypothesized that tissue necrosis is an activator of dendritic cells (DCs), which control tolerance to self-antigens. DC subsets of a murine healthy heart consisted of IRF8-dependent conventional (c)DC1, IRF4-dependent cDC2, and monocyte-derived DCs...
March 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28327905/phase-ii-study-of-idelalisib-a-selective-inhibitor-of-pi3k%C3%AE-for-relapsed-refractory-classical-hodgkin-lymphoma
#14
A K Gopal, M A Fanale, C H Moskowitz, A R Shustov, S Mitra, W Ye, A Younes, A J Moskowitz
Background: The phosphatidylinositol-3-kinase delta (PI3Kδ) inhibitor idelalisib has been shown to block downstream intracellular signaling, reduce the production of prosurvival chemokines and induce apoptosis in classical Hodgkin lymphoma (HL) cell lines. It has also been shown to inhibit regulatory T cells and myeloid-derived suppressor cells in other tumor models. We hypothesized that inhibiting PI3Kδ would have both direct and indirect antitumor effects by directly targeting the malignant cells as well as modulating the inflammatory microenvironment...
January 24, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28327619/il-36%C3%AE-signaling-controls-the-induced-regulatory-t-cell-th9-cell-balance-via-nf%C3%AE%C2%BAb-activation-and-stat-transcription-factors
#15
A Harusato, H Abo, V L Ngo, S W Yi, K Mitsutake, S Osuka, J E Kohlmeier, J D Li, A T Gewirtz, A Nusrat, T L Denning
Regulatory and effector T helper (Th) cells are abundant at mucosal surfaces, especially in the intestine, where they control the critical balance between tolerance and inflammation. However, the key factors that reciprocally dictate differentiation along these specific lineages remain incompletely understood. Here we report that the interleukin-1 (IL-1) family member IL-36γ signals through IL-36 receptor, myeloid differentiation primary response gene 88, and nuclear factor-κBp50 in CD4(+) T cells to potently inhibit Foxp3-expressing induced regulatory T cell (Treg) development, while concomitantly promoting the differentiation of Th9 cells via a IL-2-STAT5- (signal transducer and activator of transcription factor 5) and IL-4-STAT6-dependent pathway...
March 22, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28326743/dopamine-receptors-modulate-t-lymphocytes-via-inhibition-of-camp-creb-signaling-pathway
#16
(no author information available yet)
OBJECTIVES: We have previously reported that dopamine D2-like receptors including D2, D3 and D4 receptors are more important in mediating modulation of T cells than dopamine D1-like receptors (D1 and D5 receptors). Here we aimed to clarify the role of D2-like receptors in regulation of differentiation and function of T lymphocyte subsets, including helper T (Th)1, Th2, Th17 and regulatory T (Treg) cells. METHODS: Lymphocytes, separated from the mesenteric lymph nodes of mice, were stimulated with concanavalin A (Con A) and treated with the D2-like receptor agonist quinpirole or the antagonist haloperidol...
December 22, 2016: Neuro Endocrinology Letters
https://www.readbyqxmd.com/read/28326648/changes-in-expression-of-the-cd200-tolerance-signaling-molecule-and-its-receptor-cd200r-by-villus-trophoblasts-during-first-trimester-missed-abortion-and-in-chronic-histiocytic-intervillositis
#17
David A Clark, Jennifer M Dmetrichuk, Elizabeth McCready, Sukhbinder Dhesy-Thind, Jorge L Arredondo
PROBLEM: Expression of CD200 at the feto-maternal interface is associated with successful murine and human pregnancy. CD200 binding to CD200 receptors on lymphomyeloid cells suppresses inflammation and induces Tregs. CD200 receptors are also expressed on mouse and human placental trophoblast cells. What is the expression of CD200 and CD200R in human missed abortions which have preserved Treg levels and in chronic histiocytic intervillositis (CHI) where maternal inflammatory cells cause IUGR? METHODS: Immunohistiochemistry for CD200, CD200R, and Ki67 using human placental sections from missed abortions, term placenta, and CHI...
March 22, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28326080/characterization-of-the-highly-prevalent-regulatory-cd24-hi-cd38-hi-b-cell-population-in-human-cord-blood
#18
Ana Esteve-Solé, Irene Teixidó, Angela Deyà-Martínez, Jordi Yagüe, Ana M Plaza-Martín, Manel Juan, Laia Alsina
The newborn's immune system must transition from a sterile haploidentical uterus to the world full of antigens. Regulatory B-cells (Breg; broadly defined as CD19(+)CD24(hi)CD38(hi)) are tolerance promoters in the adult immune system. They can inhibit IFN-γ and IL-17 production by T-cells and are essential in different conditions, including pregnancy. Breg have still not been well characterized in umbilical cord blood, where we hypothesize that they are pivotal in the achievement of tolerance. We studied CD19(+)CD24(hi)CD38(hi) Breg in healthy umbilical cord blood (hUCB) compared to healthy peripheral adult blood (hAPB)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28325210/breast-cancer-immunology-and-immunotherapy-current-status-and-future-perspectives
#19
L de la Cruz-Merino, M Chiesa, R Caballero, F Rojo, N Palazón, F H Carrasco, V Sánchez-Margalet
Cancer immunology has gained renewed interest in the past few years due to emerging findings on mechanisms involved in tumoral immune evasion. Indisputably, immune edition is currently considered a critical hallmark of cancer. Basic research has revealed new targets which can be modulated in the clinical setting with new compounds and strategies. As recent evidence confirms, breast cancer (BC) is a complex and heterogeneous disease in which host immune responses play a substantial role. T-infiltrating lymphocytes measurement is suggested as a powerful new tool necessary to predict early BC evolution, especially in HER2-positive and triple negative subtypes...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28324830/chitinase-3-like-1-deficient-donor-splenocytes-accentuated-the-pathogenesis-of-acute-graft-versus-host-diseases-through-regulating-t-cell-expansion-and-type-i-inflammation
#20
Zengyao Li, Jian Gu, Jing Liu, Qin Zhu, Hao Lu, Yunjie Lu, Jianhua Rao, Ling Lu, Xuehao Wang
Acute graft-versus-host disease (aGVHD) is a major complication following transplantation, limiting the success of this therapy. Chitinase 3-like-1 (CHI3L1), a member of the glycosyl hydrolase 18 family, plays a critical role in bacterial infections, allergic disease and a variety of malignancies. Here, we investigated whether CHI3L1 could affect the pathogenesis of aGVHD in a mouse allo-HCT model. In this study, we show that CHI3L1 deficiency in donor T cells increased the severity of aGVHD through enhancing systemic and local inflammation...
March 16, 2017: International Immunopharmacology
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