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https://www.readbyqxmd.com/read/27911796/egr2-and-egr3-in-regulatory-t-cells-cooperatively-control-systemic-autoimmunity-through-ltbp3-mediated-tgf-%C3%AE-3-production
#1
Kaoru Morita, Tomohisa Okamura, Mariko Inoue, Toshihiko Komai, Shuzo Teruya, Yukiko Iwasaki, Shuji Sumitomo, Hirofumi Shoda, Kazuhiko Yamamoto, Keishi Fujio
Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by multiorgan inflammation induced by autoantibodies. Early growth response gene 2 (Egr2), a transcription factor essential for T-cell anergy induction, controls systemic autoimmunity in mice and humans. We have previously identified a subpopulation of CD4(+) regulatory T cells, CD4(+)CD25(-)LAG3(+) cells, that characteristically express both Egr2 and LAG3 and control mice model of lupus via TGF-β3 production. However, due to the mild phenotype of lymphocyte-specific Egr2-deficient mice, the presence of an additional regulator has been speculated...
November 30, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27853647/mini-intronic-plasmid-vaccination-elicits-tolerant-lag3-cd8-t-cells-and-inferior-antitumor-responses
#2
Viswa Teja Colluru, Christopher D Zahm, Douglas G McNeel
Increasing transgene expression has been a major focus of attempts to improve DNA vaccine-induced immunity in both preclinical studies and clinical trials. Novel mini-intronic plasmids (MIPs) have been shown to cause elevated and sustained transgene expression in vivo. We sought to test the antitumor activity of a MIP, compared to standard DNA plasmid immunization, using the tumor-specific antigen SSX2 in an HLA-A2-restricted tumor model. We found that MIP vaccination elicited a greater frequency of antigen-specific CD8(+) T cells when compared to conventional plasmid, and protected animals from subsequent tumor challenge...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27835752/chemical-components-of-respirable-particulate-matter-associated-with-emergency-hospital-admissions-for-type-2-diabetes-mellitus-in-hong-kong
#3
Shengzhi Sun, Hong Qiu, Kin-Fai Ho, Linwei Tian
BACKGROUND: Epidemiological studies have shown that short-term exposure to particulate matter (PM) mass is associated with diabetes morbidity and mortality, although inconsistencies still exist. Variation of chemical components in PM may have contributed to these inconsistencies. We hypothesize that certain components of respirable particulate matter (PM10), not simply PM10 mass, can exacerbate symptoms or cause acute complications for type 2 diabetes mellitus (T2DM). METHODS: We used a Poisson time-series model to examine the association between 17 chemical components of PM10 and daily emergency hospital admissions for T2DM among residents aged 65years or above from January 1998 to December 2007 in Hong Kong...
October 27, 2016: Environment International
https://www.readbyqxmd.com/read/27806296/opposing-development-of-cytotoxic-and-follicular-helper-cd4%C3%A2-t-cells-controlled-by-the-tcf-1-bcl6-nexus
#4
Tiziano Donnarumma, George R Young, Julia Merkenschlager, Urszula Eksmond, Nadine Bongard, Stephen L Nutt, Claude Boyer, Ulf Dittmer, Vu Thuy Khanh Le-Trilling, Mirko Trilling, Wibke Bayer, George Kassiotis
CD4(+) T cells develop distinct and often contrasting helper, regulatory, or cytotoxic activities. Typically a property of CD8(+) T cells, granzyme-mediated cytotoxic T cell (CTL) potential is also exerted by CD4(+) T cells. However, the conditions that induce CD4(+) CTLs are not entirely understood. Using single-cell transcriptional profiling, we uncover a unique signature of Granzyme B (GzmB)(+) CD4(+) CTLs, which distinguishes them from other CD4(+) T helper (Th) cells, including Th1 cells, and strongly contrasts with the follicular helper T (Tfh) cell signature...
November 1, 2016: Cell Reports
https://www.readbyqxmd.com/read/27777974/lymphocyte-activation-gene-3-and-coronary-artery-disease
#5
Diana Golden, Antonina Kolmakova, Sunitha Sura, Anthony T Vella, Ani Manichaikul, Xin-Qun Wang, Suzette J Bielinski, Kent D Taylor, Yii-Der Ida Chen, Stephen S Rich, Annabelle Rodriguez
BACKGROUND: The lipoprotein scavenger receptor BI (SCARB1) rs10846744 noncoding variant is significantly associated with atherosclerotic disease independently of traditional cardiovascular risk factors. We identified a potentially novel connection between rs10846744, the immune checkpoint inhibitor lymphocyte activation gene 3 (LAG3), and atherosclerosis. METHODS: In vitro approaches included flow cytometry, lipid raft isolation, phosphosignaling, cytokine measurements, and overexpressing and silencing LAG3 protein...
October 20, 2016: JCI Insight
https://www.readbyqxmd.com/read/27767033/parkinson-disease-lag3-facilitates-cell-to-cell-spread-of-%C3%AE-synuclein-pathology
#6
Heather Wood
No abstract text is available yet for this article.
October 21, 2016: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/27708076/pathological-%C3%AE-synuclein-transmission-initiated-by-binding-lymphocyte-activation-gene-3
#7
Xiaobo Mao, Michael Tianhao Ou, Senthilkumar S Karuppagounder, Tae-In Kam, Xiling Yin, Yulan Xiong, Preston Ge, George Essien Umanah, Saurav Brahmachari, Joo-Ho Shin, Ho Chul Kang, Jianmin Zhang, Jinchong Xu, Rong Chen, Hyejin Park, Shaida A Andrabi, Sung Ung Kang, Rafaella Araújo Gonçalves, Yu Liang, Shu Zhang, Chen Qi, Sharon Lam, James A Keiler, Joel Tyson, Donghoon Kim, Nikhil Panicker, Seung Pil Yun, Creg J Workman, Dario A A Vignali, Valina L Dawson, Han Seok Ko, Ted M Dawson
Emerging evidence indicates that the pathogenesis of Parkinson's disease (PD) may be due to cell-to-cell transmission of misfolded preformed fibrils (PFF) of α-synuclein (α-syn). The mechanism by which α-syn PFF spreads from neuron to neuron is not known. Here, we show that LAG3 (lymphocyte-activation gene 3) binds α-syn PFF with high affinity (dissociation constant = 77 nanomolar), whereas the α-syn monomer exhibited minimal binding. α-Syn-biotin PFF binding to LAG3 initiated α-syn PFF endocytosis, transmission, and toxicity...
September 30, 2016: Science
https://www.readbyqxmd.com/read/27697383/acute-exposure-to-fine-particulate-matter-and-cardiovascular-hospital-emergency-room-visits-in-beijing-china
#8
Qin Xu, Shuo Wang, Yuming Guo, Chao Wang, Fangfang Huang, Xia Li, Qi Gao, Lijuan Wu, Lixin Tao, Jin Guo, Wei Wang, Xiuhua Guo
Fine particulate matter (PM2.5) air pollution outbreaks have recently occurred frequently in China. However, evidence of the associations between short-term exposure to PM2.5 and cardiovascular morbidity is still limited in China. This study aimed to evaluate the associations between PM2.5 and hospital emergency room visits (ERVs) for cardiovascular diseases in urban areas in Beijing. Daily counts of cardiovascular ERVs were collected from ten large general hospitals from Jan 1 to Dec 31, 2013. Air pollution data were obtained from the Beijing Environmental Protection Bureau including 17 monitoring stations...
January 2017: Environmental Pollution
https://www.readbyqxmd.com/read/27581189/novel-foxp3-il-10-regulatory-t-cells-induced-by-b-cells-alleviate-intestinal-inflammation-in-vivo
#9
Tzu-Yu Shao, Ling-Hui Hsu, Chien-Hui Chien, Bor-Luen Chiang
Recent studies have revealed various Foxp3(-) regulatory T (Treg) cell subsets effectively protect mice from colitis. In the present study, we demonstrated that B cells induced a particular subset of regulatory T (Treg-of-B) cells, expressing programmed cell death 1 (PD-1), inducible costimulator (ICOS), lymphocyte-activation gene 3 (LAG3), glucocorticoid-induced tumor necrosis factor receptor (GITR), and OX-40, did not express Foxp3. Treg-of-B cells produced abundant levels of IL-10 and low levels of IL-4 and TGF-β...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27565576/functional-exhaustion-of-cd4-t-cells-induced-by-co-stimulatory-signals-from-myeloid-leukaemia-cells
#10
Didem Ozkazanc, Digdem Yoyen-Ermis, Ece Tavukcuoglu, Yahya Buyukasik, Gunes Esendagli
To cope with immune responses, tumour cells implement elaborate strategies such as adaptive resistance and induction of T-cell exhaustion. T-cell exhaustion has been identified as a state of hyporesponsiveness that arises under continuous antigenic stimulus. Nevertheless, contribution of co-stimulatory molecules to T-cell exhaustion in cancer remains to be better defined. This study explores the role of myeloid leukaemia-derived co-stimulatory signals on CD4(+) T helper (Th) cell exhaustion, which may limit anti-tumour immunity...
December 2016: Immunology
https://www.readbyqxmd.com/read/27500645/sex-steroid-induced-dna-methylation-changes-and-inflammation-response-in-prostate-cancer
#11
Songping Wang, Pamela A G Clarke, Roderick Davis, Salma Mumuni, Bernard Kwabi-Addo
Sex steroid hormones have been reported to induce inflammation causing dysregulation of cytokines in prostate cancer cells. However, the underlying epigenetic mechanism has not well been studied. The objective of this study was to evaluate the effect of sex steroid hormones on epigenetic DNA methylation changes in prostate cancer cells using a signature PCR methylation array panel that correspond to 96 genes with biological function in the human inflammatory and autoimmune signals in prostate cancer. Of the 96-gene panel, 32 genes showed at least 10% differentially methylation level in response to hormonal treatment when compared to untreated cells...
October 2016: Cytokine
https://www.readbyqxmd.com/read/27458246/antitumor-effect-of-programmed-death-1-pd-1-blockade-in-humanized-the-nog-mhc-double-knockout-mouse
#12
Tadashi Ashizawa, Akira Iizuka, Chizu Nonomura, Ryota Kondou, Chie Maeda, Haruo Miyata, Takashi Sugino, Koichi Mitsuya, Nakamasa Hayashi, Yoko Nakasu, Kouji Maruyama, Ken Yamaguchi, Ikumi Katano, Mamoru Ito, Yasuto Akiyama
PURPOSE: Humanized mouse models using NOD/Shi-scid-IL2rγ(null) (NOG) and NOD/LtSz-scid IL2rγ(null) (NSG) mouse are associated with several limitations, such as long incubation time for stem cell engraftment and the development of xenograft versus host disease in mice injected with peripheral blood mononuclear cells (PBMCs). To solve problems, we used humanized major histocompatibility class I- and class II-deficient NOG mice (referred to as NOG-dKO) to evaluate the antitumor effect of anti-programmed death-1 (PD-1) antibody...
July 25, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27413045/particulate-matter-and-hospital-admissions-for-stroke-in-beijing-china-modification-effects-by-ambient-temperature
#13
Fangfang Huang, Yanxia Luo, Yuming Guo, Lixin Tao, Qin Xu, Chao Wang, Anxin Wang, Xia Li, Jin Guo, Aoshuang Yan, Xiuhua Guo
BACKGROUND: The impact of particulate matter (PM) on stroke may vary by particle size, stroke subtype, and patient characteristics and temperature. We examined the association of stroke admissions with PM in different subgroups in Beijing, China, during 2013-2014. METHODS AND RESULTS: A time-stratified case-crossover design was used to assess the relation between PM of different particle sizes and hospital admissions for ischemic and hemorrhagic stroke. Stratified analyses were performed by age, sex, and temperature...
July 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/27339628/prognostic-relevance-of-genetic-variants-involved-in-immune-checkpoints-in-patients-with-colorectal-cancer
#14
Shinkyo Yoon, Byung Woog Kang, Su Yeon Park, Hye Jin Kim, Jun Seok Park, Gyu Seog Choi, Jong Gwang Kim
PURPOSE: Genetic polymorphisms in genes involved in the immune response are already known to affect the anti-tumor immune response. This study systematically investigated the association of 14 functional SNPs in a panel of 7 genes (CCL2, CCR2, NT5E, IDO1, LAG3, PDL1, and PDCD1) involved in immune response checkpoints with the survival outcomes of Korean patients with colorectal cancer (CRC). METHODS: The genomic DNA from 668 patients with curatively resected CRC was analyzed using a Sequenom MassARRAY, along with the association with recurrence-free survival (RFS) and overall survival (OS)...
August 2016: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/27256343/pathways-and-gene-networks-mediating-the-regulatory-effects-of-cannabidiol-a-nonpsychoactive-cannabinoid-in-autoimmune-t-cells
#15
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/27249753/immunotherapy-beyond-anti-pd-1-and-anti-pd-l1-therapies
#16
Scott J Antonia, Johan F Vansteenkiste, Edmund Moon
Advanced-stage non-small cell lung cancer (NSCLC) and small cell lung cancer are cancers in which chemotherapy produces a survival benefit, although it is small. We now know that anti-PD-1/PD-L1 has substantial clinical activity in both of these diseases, with an overall response rate (ORR) of 15%-20%. These responses are frequently rapid and durable, increase median overall survival (OS) compared with chemotherapy, and produce long-term survivors. Despite these very significant results, many patients do not benefit from anti-PD-1/PD-L1...
2016: American Society of Clinical Oncology Educational Book
https://www.readbyqxmd.com/read/27241062/genetic-variations-in-immunomodulatory-pathways-to-predict-survival-in-patients-with-locoregional-gastric-cancer
#17
Y Sunakawa, S Cao, N B Volz, M D Berger, D Yang, A Parekh, W Zhang, S Matsusaka, Y Ning, S Stremitzer, S Stintzing, A Sebio, S Okazaki, T Wakatsuki, M Azuma, M Watanabe, W Koizumi, A H Wu, H-J Lenz
Immunomodulator-targeting therapies are under development in gastric cancer (GC). However, the role of genes modulating anti-tumor immunity in GC remains poorly understood. We investigated the association of variations in genes involved in immunomodulatory pathways with overall survival (OS) in locoregional GC patients. Extracted genomic DNA was analyzed for 35 functional single-nucleotide polymorphisms in genes, PDCD1, CD274, CTLA4, FOXP3, LAG3, ADORA2A, NT5E and IDO1, in 162 Japanese patients as discovery set and 277 US patients as validation set...
May 31, 2016: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/27198196/gut-environment-induced-intraepithelial-autoreactive-cd4-t-cells-suppress-central-nervous-system-autoimmunity-via-lag-3
#18
Atsushi Kadowaki, Sachiko Miyake, Ryoko Saga, Asako Chiba, Hideki Mochizuki, Takashi Yamamura
The gut environment has been found to significantly influence autoimmune diseases such as multiple sclerosis; however, immune cell mechanisms are unclear. Here we show that the gut epithelium of myelin oligodendrocyte glycoprotein(35-55)-specific T-cell receptor transgenic mice contains environmental stimuli-induced intraepithelial lymphocytes (IELs) that inhibit experimental autoimmune encephalomyelitis on transfer. These cells express surface markers phenotypical of 'induced' IELs, have a TH17-like profile and infiltrate the central nervous system (CNS)...
May 20, 2016: Nature Communications
https://www.readbyqxmd.com/read/27197067/molecular-drivers-of-the-non-t-cell-inflamed-tumor-microenvironment-in-urothelial-bladder-cancer
#19
Randy F Sweis, Stefani Spranger, Riyue Bao, Gladell P Paner, Walter M Stadler, Gary Steinberg, Thomas F Gajewski
Muscle-invasive urothelial bladder cancer is a common malignancy with poor outcomes for which immune checkpoint blockade is now showing promise. Despite clinical activity of PD-1/PD-L1-targeted therapy in this disease, most patients do not benefit and resistance mechanisms remain unknown. The non-T-cell-inflamed tumor microenvironment correlates with poor prognosis and resistance to immunotherapies. In this study, we determined tumor-oncogenic pathways correlating with T-cell exclusion. We first establish in this report that T-cell-inflamed bladder tumors can be identified by immune gene expression profiling with concordance with CD8(+) T-cell infiltration...
July 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27108398/cd4-t-cell-gene-expression-of-healthy-donors-hiv-1-and-elite-controllers-immunological-chaos
#20
G Nunnari, P Fagone, F Condorelli, F Nicoletti, L Malaguarnera, M Di Rosa
OBJECTIVES: T-cell repertoire dysfunction characterizes human immunodeficiency virus type 1 (HIV-1) infection, but the pathogenic mechanisms remain unclear. Disease progression is probably due to a profound dysregulation of Th1, Th2, Th17 and Treg patterns. The aim of this study was to analyze the features of CD4+ T cells in HIV-positive patients with different viroimmunological profile. METHODS: we used a gene expression dataset of CD4+ T cells from healthy donors, HIV+ naive patients and Elite Controllers (EC), obtained from the NCBI Gene Expression Omnibus (GEO, http://www...
July 2016: Cytokine
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