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https://www.readbyqxmd.com/read/29055015/small-molecule%C3%A2-inhibition-of-pd-1-transcription-is-an-effective-alternative-to-antibody-blockade-in-cancer-therapy
#1
Alison Taylor, David Rothstein, Christopher E Rudd
The impact of PD-1 immune checkpoint therapy prompts exploration of other strategies to downregulate PD-1 for cancer therapy. We previously showed that the serine/threonine kinase, glycogen synthase kinase GSK-3α/β, is a central regulator of PD-1 transcription in CD8+ T cells. Here, we show that the use of small molecule inhibitors of GSK-3α/β (GSK-3i) to reduce pcdc1 (PD-1) transcription and expression was as effective as anti-PD-1 and PDL-1 blocking antibodies in the control of B16 melanoma, or EL4 lymphoma, in primary tumor and metastatic settings...
October 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/29054490/cd21-lo-med-cd27-proinflammatory-b-cells-are-enriched-in-breast-cancer-patients-and-promote-antitumor-t-cell-responses
#2
Shiguang Zhu, Xingmiao Wang, Ji Wang, Jun Lin, Yizi Cong, Guangdong Qiao
Breast cancer is a common malignancy and a major cause of death in women worldwide. The immunomodulatory role of B cells is being increasingly recognized in autoimmune diseases and cancers. In recent years, immunotherapeutic strategies that upregulate the patient's own antitumor T cell responses have shown promise in treating solid tumors and are being developed for breast cancer. In this study, we discovered that the B cells in breast cancer patients were enriched with interferon (IFN)-γ-expressing cells and presented high potency for IFN-γ production...
October 18, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28969068/aberrant-dna-methylation-of-gata-binding-protein-3-gata3-interleukin-4-il-4-and-transforming-growth-factor-%C3%AE-tgf-%C3%AE-promoters-in-behcet-s-disease
#3
Yunyun Zhu, Yiguo Qiu, Hongsong Yu, Shenglan Yi, Wencheng Su, Aize Kijlstra, Peizeng Yang
The pathogenesis of Behcet's disease (BD) remains poorly understood. The purpose of this study was to investigate whether an aberrant DNA methylation of transcriptional and inflammatory factors, including TBX21, GATA3, RORγt, FOXP3, IFN-γ, IL-4, IL-17A and TGF-β, in CD4(+)T confers risk to BD. We found that the promoter methylation level of GATA3, IL-4 and TGF-β was significantly up-regulated in active BD patients and negatively correlated with the corresponding mRNA expression. The mRNA expression of GATA3 and TGF-β was markedly down-regulated in active BD patients compared to healthy individuals...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28894104/nfatc1-controls-the-cytotoxicity-of-cd8-t-cells
#4
Stefan Klein-Hessling, Khalid Muhammad, Matthias Klein, Tobias Pusch, Ronald Rudolf, Jessica Flöter, Musga Qureischi, Andreas Beilhack, Martin Vaeth, Carsten Kummerow, Christian Backes, Rouven Schoppmeyer, Ulrike Hahn, Markus Hoth, Tobias Bopp, Friederike Berberich-Siebelt, Amiya Patra, Andris Avots, Nora Müller, Almut Schulze, Edgar Serfling
Cytotoxic T lymphocytes are effector CD8(+) T cells that eradicate infected and malignant cells. Here we show that the transcription factor NFATc1 controls the cytotoxicity of mouse cytotoxic T lymphocytes. Activation of Nfatc1 (-/-) cytotoxic T lymphocytes showed a defective cytoskeleton organization and recruitment of cytosolic organelles to immunological synapses. These cells have reduced cytotoxicity against tumor cells, and mice with NFATc1-deficient T cells are defective in controlling Listeria infection...
September 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/28822698/staphylococcus-aureus-from-atopic-dermatitis-skin-alters-cytokine-production-triggered-by-monocyte-derived-langerhans-cell
#5
Kazumasa Iwamoto, Masaya Moriwaki, Yoshie Niitsu, Masachika Saino, Shunsuke Takahagi, Junzo Hisatsune, Motoyuki Sugai, Michihiro Hide
BACKGROUND: Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases. The skin of patients with AD presents as a disbalance of the microbiome with a strong colonization by Staphylococcus aureus, which positively correlates with the severity of the disease. However, the effect of colonized S. aureus on the skin immune system has not been fully elucidated. OBJECTIVE: The aim of this study is to explore whether S. aureus isolated from AD skin is able to skew T cell responses via Langerhans cells (LC) as compared to a standard strain of S...
August 5, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28815219/conventional-nk-cells-and-ilc1-are-partially-ablated-in-the-livers-of-ncr1-icre-tbx21-fl-fl-mice
#6
Antonia O Cuff, Victoria Male
Mouse liver contains both Eomes-dependent conventional natural killer (cNK) cells and Tbet-dependent liver-resident type I innate lymphoid cells (ILC1). In order to better understand the role of ILC1, we attempted to generate mice that would lack liver ILC1, while retaining cNK, by conditional deletion of Tbet in NKp46+ cells. Here we report that the Ncr1 (iCre)Tbx21 (fl/fl) mouse has a roughly equivalent reduction in both the cNK and ILC1 compartments of the liver, limiting its utility for investigating the relative contributions of these two cell types in disease models...
2017: Wellcome Open Research
https://www.readbyqxmd.com/read/28807314/a-candidate-gene-approach-to-study-nematode-resistance-traits-in-naturally-infected-sheep
#7
Hazel Wilkie, Valentina Riggio, Oswald Matika, Louise Nicol, Kathryn A Watt, Rona Sinclair, Alexandra M Sparks, Daniel H Nussey, Josephine M Pemberton, Ross D Houston, John Hopkins
Sheep naturally acquire a degree of resistant immunity to parasitic worm infection through repeated exposure. However, the immune response and clinical outcome vary greatly between animals. Genetic polymorphisms in genes integral to differential T helper cell polarization may contribute to variation in host response and disease outcome. A total of twelve single nucleotide polymorphisms (SNPs) were sequenced in IL23R, RORC2 and TBX21 from genomic DNA of Scottish Blackface lambs. Of the twelve SNPs, six were non-synonymous (missense), four were within the 3' UTRs and two were intronic...
August 30, 2017: Veterinary Parasitology
https://www.readbyqxmd.com/read/28801624/stingray-venom-activates-il-33-producing-cardiomyocytes-but-not-mast-cell-to-promote-acute-neutrophil-mediated-injury
#8
Janaina Cardoso Dos Santos, Lidiane Zito Grund, Carla Simone Seibert, Elineide Eugênio Marques, Anderson Brito Soares, Valerie F Quesniaux, Bernhard Ryffel, Monica Lopes-Ferreira, Carla Lima
One of the hallmarks of acute inflammation is neutrophil infiltration of tissues. We investigated molecular mechanisms implicated in acute neutrophilic inflammation induced by the venom of a freshwater stingray (Potamotrygon cf. henlei) in mice. Ray venom induced early mobilization of neutrophil in the microvasculature of cremaster mice and infiltration of the peritoneal cavity 2 hours after injury, in a dose-response manner. IL-1β, IL-6, TNF-α, and KC were produced. The neutrophilic infiltration did not occur in mice with ST2 receptor and MyD88 adapters neutralized, or in those with PI3K and p38 MAPK signaling blocked...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729226/solanum-paniculatum-l-decreases-levels-of-inflammatory-cytokines-by-reducing-nfkb-tbet-and-gata3-gene-expression-in-vitro
#9
Raimon Rios, Hugo Bernardino Ferreira da Silva, Norma Vilany Queiroz Carneiro, Anaque de Oliveira Pires, Tamires Cana Brasil Carneiro, Ryan Dos Santos Costa, Cintia Rodrigues Marques, Marta Santos Serafim Machado, Eudes da Silva Velozo, Telma M G da Silva, Tania M S da Silva, Adilva de Souza Conceição, Neuza Maria Alcântara-Neves, Camila Alexandrina Figueiredo
ETHNOPHARMACOLOGICAL RELEVANCE: Solanum paniculatum L., popularly known as jurubeba, is a common subtropical plant from Brazil, Paraguay, Bolivia and Argentina, that is used in folk medicine for the treatment of anemia, gastrointestinal disorders and inflammatory conditions in general. In addition to that, an ethnobotanical survey in "Todos os Santos" Bay have pointed out S. paniculatum as an herb to treat asthma. Previous publications have shown that S. paniculatum possesses antibiotic, antioxidant and modulatory effects on gastric acid secretion; however, its anti-inflammatory potential remains unexplored...
July 18, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28666864/spv-locus-aggravates-salmonella-infection-of-zebrafish-adult-by-inducing-th1-th2-shift-to-th2-polarization
#10
Shu-Yan Wu, Li-Dan Wang, Guang-Mei Xu, Si-di Yang, Qi-Feng Deng, Yuan-Yuan Li, Rui Huang
Salmonella enterica serovar typhimurium (S. typhimurium) are facultative intracellular enteric pathogens causing disease with a broad range of hosts. It was known that Th1-type cytokines such as IFN-γ, IL-12, and TNF-α etc. could induce protective immunity against intracellular pathogens, while Th2-type cytokines such as IL-4, IL-10, and IL-13 etc. are proved to help pathogens survive inside hosts and cause severe infection. One of the critical virulence factor attributes to the pathogenesis of S. typhimurium is Salmonella plasmid virulence genes (spv)...
August 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28658564/a-clustering-approach-to-identify-and-characterize-the-asthma-and-chronic-obstructive-pulmonary-disease-overlap-phenotype
#11
K Hirai, T Shirai, M Suzuki, T Akamatsu, T Suzuki, I Hayashi, A Yamamoto, T Akita, S Morita, K Asada, D Tsuji, K Inoue, K Itoh
BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous diseases. The phenotypes that have clinical features of both asthma and COPD are still incompletely understood. OBJECTIVE: To clarify the best discriminators of the asthma-COPD overlap phenotype from asthma and COPD subgroups using a clustering approach. METHODS: This study assessed pathophysiological parameters, including mRNA expression levels of T helper cell-related transcription factors, namely TBX21 (Th1), GATA3 (Th2), RORC (Th17) and FOXP3 (Treg), in peripheral blood mononuclear cells in asthma patients (n=152) and in COPD patients (n=50)...
November 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28615725/transcriptome-analysis-reveals-similarities-between-human-blood-cd3-cd56-bright-cells-and-mouse-cd127-innate-lymphoid-cells
#12
David S J Allan, Ana Sofia Cerdeira, Anuisa Ranjan, Christina L Kirkham, Oscar A Aguilar, Miho Tanaka, Richard W Childs, Cynthia E Dunbar, Jack L Strominger, Hernan D Kopcow, James R Carlyle
For many years, human peripheral blood natural killer (NK) cells have been divided into functionally distinct CD3(-) CD56(bright) CD16(-) and CD3(-) CD56(dim) CD16(+) subsets. Recently, several groups of innate lymphoid cells (ILC), distinct from NK cells in development and function, have been defined in mouse. A signature of genes present in mouse ILC except NK cells, defined by Immunological Genome Project studies, is significantly over-represented in human CD56(bright) cells, by gene set enrichment analysis...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28586108/bcl6-promotes-follicular-helper-t-cell-differentiation-and-pd-1-expression-in-a-blimp1-independent-manner-in-mice
#13
Markus M Xie, Byung-Hee Koh, Kristin Hollister, Hao Wu, Jie Sun, Mark H Kaplan, Alexander L Dent
The transcription factors Bcl6 and Blimp1 have opposing roles in the development of the follicular helper T (TFH ) cells: Bcl6 promotes and Blimp1 inhibits TFH -cell differentiation. Similarly, Bcl6 activates, while Blimp1 represses, expression of the TFH -cell marker PD-1. However, Bcl6 and Blimp1 repress each other's expression, complicating the interpretation of the regulatory network. Here we sought to clarify the extent to which Bcl6 and Blimp1 independently control TFH -cell differentiation by generating mice with T-cell specific deletion of both Bcl6 and Blimp1 (double conditional KO [dcKO] mice)...
July 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28550044/t-cells-lacking-hdac11-have-increased-effector-functions-and-mediate-enhanced-alloreactivity-in-a-murine-model
#14
David M Woods, Karrune V Woan, Fengdong Cheng, Andressa L Sodré, Dapeng Wang, Yongxia Wu, Zi Wang, Jie Chen, John Powers, Javier Pinilla-Ibarz, Yu Yu, Ya Zhang, Xuefeng Wu, Xiaoyan Zheng, Jeffrey Weber, Wayne W Hancock, Edward Seto, Alejandro Villagra, Xue-Zhong Yu, Eduardo M Sotomayor
Histone acetylation and the families of enzymes responsible for controlling these epigenetic marks have been implicated in regulating T-cell maturation and phenotype. Here, we demonstrate a previously undefined role of histone deacetylase 11 (HDAC11) in regulating T-cell effector functions. Using EGFP-HDAC11 transgenic reporter mice, we found that HDAC11 expression was lower in effector relative to naive and central memory T-cell populations, and activation of resting T cells resulted in its decreased expression...
July 13, 2017: Blood
https://www.readbyqxmd.com/read/28488961/effect-of-storage-period-of-red-blood-cell-suspensions-on-helper-t-cell-subpopulations
#15
Salih H Bal, Yasemin Heper, Levent T Kumaş, Furkan Guvenc, Ferah Budak, Güher Göral, Haluk B Oral
BACKGROUND: The aim of this study was to investigate the immunological alterations that occur during the storage of erythrocyte suspensions which may lead to transfusion-related immunomodulation following allogeneic blood transfusion. MATERIALS AND METHODS: One part of the erythrocyte suspensions obtained from donors was leucoreduced while the other part was not. The leucoreduced (LR) and non-leucoreduced (NL) erythrocyte suspensions were then further divided into three equal amounts which were stored for 0, 21 or 42 days prior to measurements, by enzyme-linked immunosorbent assays, of cytokine levels in their supernatants...
March 15, 2017: Blood Transfusion, Trasfusione del Sangue
https://www.readbyqxmd.com/read/28473623/tbet-is-a-critical-modulator-of-foxp3-expression-in-autoimmune-graft-versus-host-disease
#16
Shoba Amarnath, Arian Laurence, Nathaniel Zhu, Renato Cunha, Michael A Eckhaus, Samuel Taylor, Jason E Foley, Monalisa Ghosh, Tania C Felizardo, Daniel H Fowler
CD4(+) T-helper subsets drive autoimmune chronic graft-versus-host disease, a major complication after allogeneic bone marrow transplantation. However, it remains unclear how specific T-helper subsets contribute to chronic graft-versus-host disease. T-helper type 1 cells are one of the major disease-mediating T-cell subsets and require interferon-γ signaling and Tbet expression for their function. Regulatory T cells on the other hand can inhibit T-helper type 1 cell-mediated responses. Using an established murine model that isolates the autoimmune component of graft-versus-host disease, we hypothesized that T-helper type 1 cells would restrict FoxP3-driven regulatory T cells...
August 2017: Haematologica
https://www.readbyqxmd.com/read/28470472/impact-of-intra-tumoral-il17a-and-il32-gene-expression-on-t-cell-responses-and-lymph-node-status-in-breast-cancer-patients
#17
Shreyas Bhat, Nilesh Gardi, Sujata Hake, Nirupama Kotian, Sharada Sawant, Sadhana Kannan, Vani Parmar, Sangeeta Desai, Amit Dutt, Narendra N Joshi
PURPOSE: Pro-inflammatory cytokines such as Interleukin-17A (IL17A) and Interleukin-32 (IL32), known to enhance natural killer and T cell responses, are also elevated in human malignancies and linked to poor clinical outcomes. To address this paradox, we evaluated relation between IL17A and IL32 expression and other inflammation- and T cell response-associated genes in breast tumors. METHODS: TaqMan-based gene expression analysis was carried out in seventy-eight breast tumors...
May 3, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28408751/mmp9-integrates-multiple-immunoregulatory-pathways-that-discriminate-high-suppressive-activity-of-human-mesenchymal-stem-cells
#18
Carolina Lavini-Ramos, Hernandez Moura Silva, Alessandra Soares-Schanoski, Sandra Maria Monteiro, Ludmila Rodrigues Pinto Ferreira, Ana Paula Pacanaro, Samirah Gomes, Janaína Batista, Kellen Faé, Jorge Kalil, Verônica Coelho
The mechanisms underlying mesenchymal stem cells' (MSC) suppressive potency are largely unknown. We here show that highly suppressive human adipose tissue-derived MSC (AdMSC) display and induce a differential immunologic profile, upon ongoing AdMSC suppressive activity, promoting: (i) early correlated inhibition of IFN-γ and TNF-α production, along IL-10 increase, (ii) CD73(+)Foxp3(+)Treg subset expansion, and (iii) specific correlations between gene expression increases, such as: MMP9 correlated with CCL22, TNF, FASL, RUNX3, and SEMAD4 in AdMSC and, in T cells, MMP9 upregulation correlated with CCR4, IL4 and TBX21, among others, whereas MMP2 correlated with BCL2 and LRRC31...
April 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28380410/quercetin-exhibits-adjuvant-activity-by-enhancing-th2-immune-response-in-ovalbumin-immunized-mice
#19
Divya Singh, Himanshi Tanwar, Bindhya Jayashankar, Jyoti Sharma, Swetha Murthy, Sudipta Chanda, Shashi Bala Singh, Lilly Ganju
Quercetin, one of the most abundant of plant flavonoids, has been studied with a great deal of attention over the last several decades mainly for its properties in inflammation and allergy. In this study, we are reporting for the first time the in vivo immunostimulatory activity of quercetin in ovalbumin immunized Balb/c mice. Administration of quercetin (50mg/kg body weight) along with ovalbumin antigen showed increased ovalbumin specific serum IgG antibody titres in comparison to the control group (p<0...
June 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28379390/arid5a-deficient-mice-are-highly-resistant-to-bleomycin-induced-lung-injury
#20
Praveen Kumar Dubey, Kazuya Masuda, Kishan Kumar Nyati, Mohammad Mahabub -Uz Zaman, Jaya Prakash Chalise, David Millrine, Wang Kai, Barry Ripley, Tadamitsu Kishimoto
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are among the major causes of death worldwide due to acute inflammation in the lung. AT-rich interactive domain-containing 5a (Arid5a) is an RNA-binding protein involved in inflammatory autoimmune disease through post-transcriptional control of Il6, Stat3 and Tbx21 gene expression. We found that Arid5a-deficient mice were highly refractory to bleomycin (BLM)-induced lethality. Arid5a deficiency suppressed lung pathology, cytokine production (especially, IL-6), and clinical symptoms in BLM-treated mice...
February 1, 2017: International Immunology
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