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https://www.readbyqxmd.com/read/28325871/progression-of-type-1-diabetes-from-the-prediabetic-stage-is-controlled-by-interferon-%C3%AE-signaling
#1
Brett S Marro, Brian C Ware, Jaroslav Zak, Juan Carlos de la Torre, Hugh Rosen, Michael B A Oldstone
Blockade of IFN-α but not IFN-β signaling using either an antibody or a selective S1PR1 agonist, CYM-5442, prevented type 1 diabetes (T1D) in the mouse Rip-LCMV T1D model. First, treatment with antibody or CYM-5442 limited the migration of autoimmune "antiself" T cells to the external boundaries around the islets and prevented their entry into the islets so they could not be positioned to engage, kill, and thus remove insulin-producing β cells. Second, CYM-5442 induced an exhaustion signature in antiself T cells by up-regulating the negative immune regulator receptor genes Pdcd1, Lag3, Ctla4, Tigit, and Btla, thereby limiting their killing ability...
March 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28325534/association-between-meteorological-factors-and-hepatitis-a-in-spain-2010-2014
#2
Pedro Gullón, Carmen Varela, Elena Vanessa Martínez, Diana Gómez-Barroso
BACKGROUND: There is growing concern of how climate change could affect public health, due to the increase number of extreme climate events. Hence, the study of the role that climate events play on the distribution of waterborne diseases, like Hepatitis A, could be key for developing new prevention approaches. OBJECTIVE: To investigate the association between climate factors and Hepatitis A in Spain between 2010 and 2014. METHODS: Weekly Hepatitis A cases between 2010 and 2014 were obtained from the Spanish Epidemiology Surveillance Network...
March 18, 2017: Environment International
https://www.readbyqxmd.com/read/28277274/therapeutic-reversal-of-food-allergen-sensitivity-by-mature-retinoic-acid-differentiated-dendritic-cell-induction-of-lag3-cd49b-foxp3-regulatory-t%C3%A2-cells
#3
Wojciech Dawicki, Chunyan Li, Jennifer Town, Xiaobei Zhang, John R Gordon
BACKGROUND: Anaphylaxis is a life-threatening condition for which we have limited therapeutic options. Although specific immunotherapy for food allergies is becoming more effective, it is still laborious and carries substantial risk of adverse events. On the other hand, regulatory dendritic cell (DC) therapy is effective in mouse models of allergic disease and has been shown to work with TH2 cells from atopic asthmatic patients. OBJECTIVE: We assessed whether DC immunotherapy could reverse food allergen sensitivity in mouse models to provide proof of concept relating to their use in the clinic...
October 20, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28270499/pd-l1-is-a-therapeutic-target-of-the-bromodomain-inhibitor-jq1-and-combined-with-hla-class-i-a-promising-prognostic-biomarker-in-neuroblastoma
#4
Ombretta Melaiu, Marco Mina, Marco Chierici, Renata Boldrini, Giuseppe Jurman, Paolo Romania, Valerio D'Alicandro, Maria Chiara Benedetti, Aurora Castellano, Tao Liu, Cesare Furlanello, Franco Locatelli, Doriana Fruci
PURPOSE: This study sought to evaluate expression of PD-L1 and HLA class I on neuroblastoma cells and PD-1 and LAG3 on tumor-infiltrating lymphocytes to better define patient risk-stratification and understand whether this tumor may benefit from therapies targeting immune-checkpoint molecules. EXPERIMENTAL DESIGN: In situ immunohistochemical staining for PD-L1, HLA class I, PD-1 and LAG3 was assessed in 77 neuroblastoma specimens, previously characterized for tumor-infiltrating T cell-density, and correlated with clinical outcome...
March 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28258692/lag3-cd223-as-a-cancer-immunotherapy-target
#5
REVIEW
Lawrence P Andrews, Ariel E Marciscano, Charles G Drake, Dario A A Vignali
Despite the impressive impact of CTLA4 and PD1-PDL1-targeted cancer immunotherapy, a large proportion of patients with many tumor types fail to respond. Consequently, the focus has shifted to targeting alternative inhibitory receptors (IRs) and suppressive mechanisms within the tumor microenvironment. Lymphocyte activation gene-3 (LAG3) (CD223) is the third IR to be targeted in the clinic, consequently garnering considerable interest and scrutiny. LAG3 upregulation is required to control overt activation and prevent the onset of autoimmunity...
March 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28154084/lymphocyte-activation-gene-3-a-novel-therapeutic-target-in-chronic-lymphocytic-leukemia
#6
Mika Shapiro, Yair Herishanu, Ben-Zion Katz, Nili Dezorella, Clare Sun, Sigi Kay, Aaron Polliack, Irit Avivi, Adrian Wiestner, Chava Perry
A novel therapeutic approach in cancer, attempting to stimulate host anti-tumor immunity, involves blocking of immune checkpoints. LAG3 is an immune checkpoint receptor expressed on activated/exhausted T-cells. When engaged by MHC class II molecules, LAG3 negatively regulates T-cell function thereby contributing to tumor escape. Intriguingly, a soluble LAG3 variant activates both immune and malignant MHC class II-presenting cells. In this study, we examined the role of LAG3 in the pathogenesis of chronic lymphocytic leukemia, an MHC class II-presenting malignancy, and show that chronic lymphocytic leukemia cells express and secrete LAG3...
February 2, 2017: Haematologica
https://www.readbyqxmd.com/read/28107871/forecasting-the-number-of-zoonotic-cutaneous-leishmaniasis-cases-in-south-of-fars-province-iran-using-seasonal-arima-time-series-method
#7
Mehdi Sharafi, Haleh Ghaem, Hamid Reza Tabatabaee, Hossein Faramarzi
OBJECTIVE: To predict the trend of cutaneous leishmaniasis and assess the relationship between the disease trend and weather variables in south of Fars province using Seasonal Autoregressive Integrated Moving Average (SARIMA) model. METHODS: The trend of cutaneous leishmaniasis was predicted using Mini tab software and SARIMA model. Besides, information about the disease and weather conditions was collected monthly based on time series design during January 2010 to March 2016...
January 2017: Asian Pacific Journal of Tropical Medicine
https://www.readbyqxmd.com/read/28052118/tgf-%C3%AE-3-inhibits-antibody-production-by-human-b-cells
#8
Yumi Tsuchida, Shuji Sumitomo, Kazuyoshi Ishigaki, Akari Suzuki, Yuta Kochi, Haruka Tsuchiya, Mineto Ota, Toshihiko Komai, Mariko Inoue, Kaoru Morita, Tomohisa Okamura, Kazuhiko Yamamoto, Keishi Fujio
TGF-β is a pleotropic cytokine involved in various biological processes. Of the three isoforms of TGF-β, TGF-β1 has long been recognized as an important inhibitory cytokine in the immune system and has been reported to inhibit B cell function in both mice and humans. Recently, it has been suggested that TGF-β3 may play an important role in the regulation of immune system in mice. Murine CD4+CD25-LAG3+ regulatory T cells suppress B cell function through the production of TGF-β3, and it has been reported that TGF-β3 is therapeutic in a mouse model of systemic lupus erythematosus...
2017: PloS One
https://www.readbyqxmd.com/read/28003742/major-air-pollutants-and-risk-of-copd-exacerbations-a-systematic-review-and-meta-analysis
#9
Jinhui Li, Shengzhi Sun, Robert Tang, Hong Qiu, Qingyuan Huang, Tonya G Mason, Linwei Tian
BACKGROUND: Short-term exposure to major air pollutants (O3, CO, NO2, SO2, PM10, and PM2.5) has been associated with respiratory risk. However, evidence on the risk of chronic obstructive pulmonary disease (COPD) exacerbations is still limited. The present study aimed at evaluating the associations between short-term exposure to major air pollutants and the risk of COPD exacerbations. METHODS: After a systematic search up until March 30, 2016, in both English and Chinese electronic databases such as PubMed, EMBASE, and CNKI, the pooled relative risks and 95% confidence intervals were estimated by using the random-effects model...
2016: International Journal of Chronic Obstructive Pulmonary Disease
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
#10
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...
December 13, 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
#11
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
#12
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...
December 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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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