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https://www.readbyqxmd.com/read/29778661/epigenetic-dysregulation-of-zeb1-is-involved-in-lmo2-promoted-t-cell-acute-lymphoblastic-leukaemia-leukaemogenesis
#1
Chao Wu, Jianjun Li, Chenchen Tian, Wen Shi, Huimin Jiang, Zhen Zhang, Hang Wang, Quansheng Zhang, Wei Sun, Peiqing Sun, Rong Xiang, Shuang Yang
T-cell acute lymphoblastic leukaemia (T-ALL) is a hematological malignancy caused by the accumulation of genomic lesions that affect the development of T-cells. ZEB1, a member of zinc finger-homeodomain family transcription factor, exhibits crucial function in promoting T-cell differentiation and potentially acts as a tumor suppressor in T-ALL. However, the molecular mechanism by which ZEB1 regulates T-ALL leukaemogenesis remains obscure. Here, we showed that oncogenic LIM only 2 (LMO2) could recruit Sap18 and HDAC1 to assemble an epigenetic regulatory complex, thus inducing histone deacetylation in ZEB1 promoter and chromatin remodeling to achieve transcriptional repression...
May 17, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29774578/the-immunobiology-of-rankl-and-myeloid-derived-suppressor-cell-activation-in-igg4-related-sclerosing-cholangitis
#2
Min Lian, Qixia Wang, Xiang Jiang, Jun Zhang, Yiran Wei, Yanmei Li, Bo Li, Weihua Chen, Haiyan Zhang, Qi Miao, Yanshen Peng, Xiao Xiao, Li Sheng, Weici Zhang, Jingyuan Fang, Ruqi Tang, M Eric Gershwin, Xiong Ma
The primary function of myeloid derived suppressor cells (MDSCs) is reflected in their immune modulatory role in several immune-mediated diseases. In IgG4-related disease (IgG4-RD), it has been hypothesized that there are selective regulatory defects that lead to a Th2 bias immune response. Herein we have taken advantage of a large cohort of patients with IgG4-related sclerosing cholangitis (IgG4-SC), the most common extra-pancreatic involvement of IgG4-RD, as well as controls consisting of primary sclerosing cholangitis (PSC), autoimmune hepatitis (AIH) and healthy volunteers, to study MDSC...
May 18, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29773895/crispr-cas9-system-targeting-regulatory-genes-of-hiv-1-inhibits-viral-replication-in-infected-t-cell-cultures
#3
Youdiil Ophinni, Mari Inoue, Tomohiro Kotaki, Masanori Kameoka
The CRISPR/Cas9 system provides a novel and promising tool for editing the HIV-1 proviral genome. We designed RNA-guided CRISPR/Cas9 targeting the HIV-1 regulatory genes tat and rev with guide RNAs (gRNA) selected from each gene based on CRISPR specificity and sequence conservation across six major HIV-1 subtypes. Each gRNA was cloned into lentiCRISPRv2 before co-transfection to create a lentiviral vector and transduction into target cells. CRISPR/Cas9 transduction into 293 T and HeLa cells stably expressing Tat and Rev proteins successfully abolished the expression of each protein relative to that in non-transduced and gRNA-absent vector-transduced cells...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29773681/decreased-expression-of-circulating-aire-and-increased-tfh-tfr-cells-in-myasthenia-gravis-patients
#4
Sijia Zhao, Jiaqi Ding, Shengyuan Wang, Chuan Li, Peng Guo, Min Zhang, Zhuyi Li
Myasthenia gravis (MG) is a rare prototypical autoimmune disorder caused by antibodies (Ab) against postsynaptic membrane proteins. Most reports have investigated the role of Autoimmune regulator gene (Aire) in thymic tissue in machianism of MG initiation. So far, the expression of Aire in human peripheral blood cells(we call it circulating Aire expression in the following passage) has not been reported. Herein, we explore the expression of Aire in peripharal blood, circulating T follicular helper (cTfh) and T follicular regulatory (cTfr) cells in MG patients...
May 17, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29770533/nctd-enhances-antitumor-immunity-of-gm-csf-prostate-cancer-cells-vaccine-by-inducing-apoptosis-of-regulatory-t-cells
#5
Lijun Mo, Xinji Zhang, Xiaojun Shi, Lili Wei, Dianpeng Zheng, Hongwei Li, Jimin Gao, Jinlong Li, Zhiming Hu
Norcantharidin (NCTD) is a promising antitumor drug with low toxicity. It was reported to be able to regulate immunity, but the mechanism is not yet clear. Here we explored whether NCTD could enhance the antitumor immunity induced by prostate cancer cells vaccine. The results in vitro study showed that NCTD induced apoptosis and inhibited proliferation of Tregs. Mechanistic research showed that NCTD inhibited Akt activation and activated FOXO1 transcription, resulting in pro-apoptotic effect. The results in vivo study showed that more tumor-infiltrating Tregs existed within peripheral blood and tumor tissue after treating with the vaccine...
May 16, 2018: Cancer Science
https://www.readbyqxmd.com/read/29769317/lysophospholipids-induce-innate-immune-transdifferentiation-of-endothelial-cells-resulting-in-prolonged-endothelial-activation
#6
Xinyuan Li, Luqiao Wang, Pu Fang, Yu Sun, Xiaohua Jiang, Hong Wang, Xiao-Feng Yang
Innate immune cells express danger-associated molecular pattern (DAMP) receptors, T-cell co-stimulation/co-inhibition receptors, and the major histocompatibility complex II (MHC-II). We have recently proposed that endothelial cells can serve as innate immune cells, but the molecular mechanisms involved still await discovery. Here, we investigated whether human aortic endothelial cells (HAECs) could be transdifferentiated into innate immune cells by exposing them to hyperlipidemia-upregulated DAMP molecules, i...
May 16, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29769264/rhoa-g17v-is-sufficient-to-induce-autoimmunity-and-promotes-t-cell-lymphomagenesis-in-mice
#7
Samuel Y Ng, Leon Brown, Kristen Stevenson, Tiffany deSouza, Jon C Aster, Abner Louissaint, David M Weinstock
Patients with angioimmunoblastic T-cell lymphoma (AITL) and other peripheral T-cell lymphomas (PTCL) that harbor features of follicular helper T (TFH) cells have a very poor prognosis. These lymphomas commonly present with paraneoplastic autoimmunity and lymphopenia. RhoA G17V mutation is present in 60% of TFH-like lymphomas but its role in tumorigenesis is poorly understood. We generated transgenic mice that express RhoA G17V under the control of murine CD4 regulatory elements at levels comparable to a heterozygous mutation (tgRhoA mice)...
May 16, 2018: Blood
https://www.readbyqxmd.com/read/29768737/providence-of-cd25-kir-cd127-foxp3-cd8-t-cell-subset-determines-the-dynamics-of-tumor-immune-surveillance
#8
Sreeparna Chakraborty, Pushpak Bhattacharjee, Abir K Panda, Kirti Kajal, Sayantan Bose, Gaurisankar Sa
CD8+ T-regulatory cells are progressively emerging as crucial components of immune system. The previous report suggests the presence of FOXP3-positive CD8+ Treg cells, similar to CD4+ Tregs, in cancer patients which produce high levels of IL10 and TGFβ for its immunosuppressive activities. At an early stage of tumor development, we have identified a subset of FOXP3-negative CD8+ CD25+ KIR+ CD127- a Treg-like subset which is essentially IFNγ-positive. However, this early induced CD8+ CD25+ CD127- T cell subset certainly distinct from the IFNγ+ CD8+ T-effecter cells...
May 16, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29766641/tailoring-the-homing-capacity-of-human-tregs-for-directed-migration-to-sites-of-th1-inflammation-or-intestinal-regions
#9
Romy E Hoeppli, Katherine N MacDonald, Pascal Leclair, Vivian C W Fung, Majid Mojibian, Jana Gillies, Seyed M R Rahavi, Andrew I M Campbell, Sanjiv K Gandhi, Anne M Pesenacker, Gregor Reid, Chinten J Lim, Megan K Levings
Cell-based therapy with CD4+ FOXP3+ Regulatory T cells (Tregs) is a promising strategy to limit organ rejection and graft-versus-host disease. Ongoing clinical applications have yet to consider how human Tregs could be modified to direct their migration to specific inflammation sites and/or tissues for more targeted immunosuppression. We show here that stable, homing-receptor-tailored human Tregs can be generated from thymic Tregs isolated from pediatric thymus or adult blood. To direct migration to Th1-inflammatory sites, addition of IFN-γ and IL-12 during Treg expansion produced suppressive, epigenetically-stable CXCR3+ TBET+ FOXP3+ Th1-Tregs...
May 15, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29766004/oral-administration-of-zataria-multiflora-extract-decreases-il-17-expression-in-perennial-allergic-rhinitis
#10
Nazila Ariaee, Jalal Ghorbani, Maryam Panahi, Mojgan Mohamadi, Javad Asili, Alireza Ranjbar, Reza Farid Hoseini, Farahzad Jabbari
Background: Rhinitis, which occurs most commonly as allergic rhinitis and affects 20% of the world's population, is a major health care burden causing significant morbidity. Considering the high prevalence of allergic rhinitis and anti-inflammatory effects of thyme, a favorite condiment, we performed a randomized clinical trial to determine whether thyme can relieve allergic rhinitis symptoms and affect the expression of TH17- and T-regulatory cell- (Treg) related cytokines IL-17, TGF-β, FOXP3, and IL-10...
April 2018: Reports of Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/29765931/decreased-breg-th17-ratio-improved-the-prognosis-of-patients-with-ulcerative-colitis
#11
Xue Bing, Liang Linlang, Chen Keyan
Objective: To investigate the effects of regulatory B (Breg) cells and T helper 17 (Th17) cells on pathogenesis of ulcerative colitis, explore the clinical significance of Breg/Th17 ratio on the prognosis of ulcerative colitis, and provide the theoretical basis for the targeted therapy, diagnosis, and prognosis of the disease. Methods: Peripheral blood and colonic mucosa were collected from patients with ulcerative colitis. Hematoxylin-eosin staining was used to observe the pathological changes of colonic mucosa...
2018: Canadian Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/29760699/tetraspanin-cd9-a-key-regulator-of-cell-adhesion-in-the-immune-system
#12
REVIEW
Raquel Reyes, Beatriz Cardeñes, Yesenia Machado-Pineda, Carlos Cabañas
The tetraspanin CD9 is expressed by all the major subsets of leukocytes (B cells, CD4+ T cells, CD8+ T cells, natural killer cells, granulocytes, monocytes and macrophages, and immature and mature dendritic cells) and also at a high level by endothelial cells. As a typical member of the tetraspanin superfamily, a prominent feature of CD9 is its propensity to engage in a multitude of interactions with other tetraspanins as well as with different transmembrane and intracellular proteins within the context of defined membranal domains termed tetraspanin-enriched microdomains (TEMs)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29760694/dissemination-of-orientia-tsutsugamushi-a-causative-agent-of-scrub-typhus-and-immunological-responses-in-the-humanized-draga-mouse
#13
Le Jiang, Erin K Morris, Rodrigo Aguilera-Olvera, Zhiwen Zhang, Teik-Chye Chan, Soumya Shashikumar, Chien-Chung Chao, Sofia A Casares, Wei-Mei Ching
Scrub typhus is caused by Orientia tsutsugamushi , an obligated intracellular bacterium that affects over one million people per year. Several mouse models have been used to study its pathogenesis, disease immunology, and for testing vaccine candidates. However, due to the intrinsic differences between the immune systems in mouse and human, these mouse models could not faithfully mimic the pathology and immunological responses developed by human patients, limiting their value in both basic and translational studies...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29755892/regional-control-of-regulatory-immune-cells-in-the-intestine
#14
Tina L Morhardt, Atsushi Hayashi, John Y Kao, Nobuhiko Kamada
Purpose of review: The intestine contains the largest compartment of immune regulatory cells which include T regulatory cells and IL-10 producing macrophages. These cell populations serve to restrain unnecessary immune responses of the intestine, which may lead to the pathogenesis of Crohn's disease or food allergy. Recent findings: This review discusses the recent findings pertaining to the functional regulation of these cells which may provide insight into novel therapies...
March 2018: Current Pathobiology Reports
https://www.readbyqxmd.com/read/29752722/a-new-cancer-immunotherapy-via-simultaneous-dc-mobilization-and-dc-targeted-ido-gene-silencing-using-an-immune-stimulatory-nanosystem
#15
Yujuan Zhang, Jiamin Fu, Yanmei Shi, Shanshan Peng, Ying Cai, Xuelin Zhan, Na Song, Yanling Liu, Zhigang Wang, Yanrong Yu, Yifan Wang, Qiaofa Shi, Yingyuan Fu, Keng Yuan, Nanjin Zhou, Rakesh Joshi, Thomas E Ichim, Weiping Min
The activity of negative immune regulatory molecules, such as indoleamine 2,3-oxygenase (IDO), significantly attenuates DC (Dendritic cells)-mediated immunotherapy. We have previously reported that knockdown of IDO using siRNA can reinstall anti-tumor immunity. However, a DC-targeted siRNA delivery system for in vivo mobilized DCs remains to be developed, while gene silencing in mobilized DCs for cancer immunotherapy has never been explored. In this study, we developed a novel DC-targeted siRNA delivery system, man-GNR-siIDO, using as a nanocarrier of siRNA specific for IDO (siIDO) and mannose (man) as a guide molecule for targeting DCs...
May 11, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29752720/prognostic-roles-for-il-2-producing-and-cd69-t-cell-subsets-in-colorectal-cancer-patients
#16
Edward S Taylor, John L McCall, Shirley Shen, Adam Girardin, Fran M Munro, Michael A Black, Kirsten A Ward-Hartstonge, Roslyn A Kemp
Tumor infiltrating T cells are a predictor of patient outcome in patients with colorectal cancer (CRC). However, many T cell populations have been associated with both poor and positive patient prognoses, indicating a need to further understand the role of different T cell subsets in CRC. In this study, the T cell infiltrate from the tumor and non-tumor bowel (NTB) was examined in 95 CRC patients using flow cytometry and associations with cancer stage and disease recurrence made. Our findings showed that IFN-γ-producing T cells were associated with positive patient outcomes, and CD69+ T cells were associated with disease recurrence...
May 11, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29752063/proteomic-analyses-of-human-regulatory-t-cells-reveal-adaptations-in-signaling-pathways-that-protect-cellular-identity
#17
Eloy Cuadrado, Maartje van den Biggelaar, Sander de Kivit, Yi-Yen Chen, Manon Slot, Ihsane Doubal, Alexander Meijer, Rene A W van Lier, Jannie Borst, Derk Amsen
To obtain a molecular definition of regulatory T (Treg) cell identity, we performed proteomics and transcriptomics on various populations of human regulatory and conventional CD4+ T (Tconv) cells. A protein expression signature was identified that defines all Treg cells, and another signature that defines effector Treg cells. These signatures could not be extrapolated from transcriptome data. Unique cell-biological and metabolic features in Treg cells were defined, as well as specific adaptations in cytokine, TCR, and costimulatory receptor signaling pathways...
May 5, 2018: Immunity
https://www.readbyqxmd.com/read/29751365/the-interplay-between-risk-and-preventive-factors-explains-why-some-children-develop-allergies-to-certain-foods-and-others-show-tolerance
#18
REVIEW
Sami Remes, Petri Kulmala
AIM: A number of studies have clarified the tolerance mechanisms and risk factors for food allergies. Our aim was to explore food allergy symptoms by target organs, together with the risk factors and how to prevent food allergies and induce tolerance. METHODS: We carried out a thorough review of studies on paediatric food allergies published in the last decade. RESULTS: Food allergy symptoms may affect the skin, nasal and oral mucosa, conjunctivae, gastrointestinal tract, or, in severe cases, the respiratory tract and cardiovascular organs...
May 11, 2018: Acta Paediatrica
https://www.readbyqxmd.com/read/29750331/salivary-gland-protective-regulatory-t-cell-dysfunction-underlies-female-specific-sialadenitis-in-the-nonobese-diabetic-mouse-model-of-sj%C3%A3-gren-syndrome
#19
Jennifer Y Barr, Xiaofang Wang, Portia A Kreiger, Scott M Lieberman
Immune cell-mediated destruction of salivary glands is a hallmark feature of Sjögren syndrome. Similar to the female predominance in humans, female nonobese diabetic (NOD) mice develop spontaneous salivary gland autoimmunity. However, in both humans and mice it is unclear what factors contribute to the initial immune infiltration of the salivary glands. Here, we used an adoptive transfer model of Sjögren syndrome to determine if female mice harbor a sex-specific defect in salivary gland-protective regulatory T (Treg) cells...
May 11, 2018: Immunology
https://www.readbyqxmd.com/read/29749611/proteomic-definition-of-human-mucosal-associated-invariant-t-cells-determines-their-unique-molecular-effector-phenotype
#20
Björn Bulitta, Werner Zuschratter, Isabel Bernal, Dunja Bruder, Frank Klawonn, Martin von Bergen, Henrikus Stephanus Paulus Garritsen, Lothar Jänsch
Mucosal-associated invariant T cells (MAIT) constitute the most abundant anti-bacterial CD8+ T cell population in humans. MR1/TCR-activated MAIT cells were reported to organize cytotoxic and innate-like responses but knowledge about their molecular effector phenotype is still fragmentary. Here, we have examined the functional inventory of human MAIT cells (CD3+Vα7.2+CD161+) in comparison with those from conventional non-MAIT CD8+ T cells (cCD8+ ) and NK cells. Quantitative mass spectrometry characterized 5500 proteins of primary MAIT cells and identified 160 and 135 proteins that discriminate them from cCD8+ T cells and NK cells donor-independently...
May 11, 2018: European Journal of Immunology
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