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T cell activation

Z Xing, H-Y Wang, W-Y Su, Y-F Liu, X-X Wang, P Zhan, T-F Lv, Y Song
OBJECTIVE: Aberrant activation of (Wingless and mouse homolog Int-1) Wnt/β-catenin signaling pathways closely involved in the occurrence and progression of several types of human malignancies. This research was undertaken to elucidate the important role of (Wingless and mouse homolog Int-1) in lung cancer. PATIENTS AND METHODS: Wnt3 expression in lung cancers and their respective normal tissues were examined by immunoblotting and immunohistochemistry. Then, Wnt3 was regulated with RNA interference (RNAi) technology in human lung cancer A549 cells, and the cell proliferation, cell cycle, cell invasion/metastasis, and apoptosis were evaluated...
March 2018: European Review for Medical and Pharmacological Sciences
Y Dong, Z-G Wang, T-S Chi
OBJECTIVE: To investigate the expression characteristics of long noncoding ribonucleic acid (lncRNA) lnc01614 in gastric cancer, so as to further investigate its roles in the occurrence and development of gastric cancer and its potential regulatory mechanism. PATIENTS AND METHODS: Quantitative Real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of lnc01614 in 79 pairs of gastric cancer tissues and normal adjacent tissues. The correlations of lnc01614 expression with pathological parameters of gastric cancer and prognoses of patients were also analyzed...
March 2018: European Review for Medical and Pharmacological Sciences
W-W Liao, C Zhang, F-R Liu, W-J Wang
OBJECTIVE: MiR-155 has been shown to be up-regulated in hepatocellular carcinoma (HCC) patients. B-cell lymphoma-2 (Bcl-2) interacting mediator of cell death (BIM) regulates cell proliferation and apoptosis, as its down-regulation is involved in HCC onset. Transcriptional factor FoxO3a mediates BIM expression and is related to HCC pathogenesis. Bioinformatics analysis showed targeted regulation of FoxO3a by miR-155. This study aims to investigate whether miR-155 plays a role in mediating FoxO3a/BIM signal pathway and HCC occurrence...
March 2018: European Review for Medical and Pharmacological Sciences
Xingye Xu, Tao Liu, Jian Yang, Lihong Chen, Bo Liu, Lingling Wang, Qi Jin
Trichophyton rubrum is the most common fungal pathogen in the world, which has been studied as an important dermatophyte model organism. Despite the prevalence of T. rubrum, the available antifungal therapies are not sufficiently efficient. In this study, we performed the first comparisons between the two major growth stages of T. rubrum: conidial and mycelial stages, based on their whole-cell proteomes and lysine acetylomes. In total, 4,343 proteins were identified in both stages, and 1,879 proteins were identified as differentially expressed between the two stages...
March 22, 2018: Journal of Proteome Research
Stephen T Keir, Vidyalakshmi Chandramohan, Carlee D Hemphill, Michael M Grandal, Maria Carlsen Melander, Mikkel W Pedersen, Ivan D Horak, Michael Kragh, Annick Desjardins, Henry S Friedman, Darell D Bigner
BACKGROUND: Sym004 is a mixture of two monoclonal antibodies (mAbs), futuximab and modotuximab, targeting non-overlapping epitopes on the epidermal growth factor receptor (EGFR). Previous studies have shown that Sym004 is more efficient at inducing internalization and degradation of EGFR than individual components, which translates into superior cancer cell inhibition. We investigated whether Sym004 induces removal of EGFRvIII and if this removal translates into tumor growth inhibition in hard-to-treat glioblastomas (GBMs) harboring the mutated, constitutively active EGFR variant III (EGFRvIII)...
March 21, 2018: Journal of Neuro-oncology
Su Huang, Yingjia Shen, Duy Pham, Li Jiang, Zheng Wang, Mark H Kaplan, Guangjun Zhang, Jie Sun
IFN regulatory factor 4 (IRF4) is a key transcription factor that promotes effector CD8+ T cell differentiation and expansion. The roles of IRF4 in regulating the CD8+ T cell response to cytokines have not been explored. In this article, we show that IL-2 and IL-15 signaling and STAT5 activation regulate IRF4 expression in CD8+ T cells. Gene-expression profile analysis has also revealed that IRF4 is required for expression of the receptors of IL-2 family cytokines CD122 and CD127. We found that IRF4 binds directly to CD122 and CD127 gene loci, indicating that it may directly promote CD122 and CD127 gene transcription...
August 1, 2017: ImmunoHorizons
Thomas Menter, Alexandar Tzankov
Purpose: Targeting cancer cells by modulating the immune system has become an important new therapeutic option in many different malignancies. Inhibition of CTLA4/B7 and PD1/PDL1 signaling is now also being investigated and already successfully applied to various hematologic malignancies. Methods: A literature review of PubMed and results of our own studies were compiled in order to give a comprehensive overview on this topic. Results: We elucidate the pathophysiological role of immunosuppressive networks in lymphomas, ranging from changes in the cellular microenvironment composition to distinct signaling pathways such as PD1/PDL1 or CTLA4/B7/CD28...
2018: Frontiers in Oncology
Yoko Motokawa, Michifumi Kokubo, Nobuo Kuwabara, Ken-Ichiro Tatematsu, Hideki Sezutsu, Hideyuki Takahashi, Koichi Sakakura, Kazuaki Chikamatsu, Shigeki Takeda
Recent clinical trials with the aim of developing tumor antigen (TA)-specific cancer vaccines against a number of malignancies have focused on the identification of TAs presented by tumor cells and recognized by T cells. In the present study, the TA melanoma antigen family A4 (MAGE-A4) protein was produced using a transgenic (TG) silkworm system. Using in vitro stimulation, it was subsequently determined whether MAGE-A4 protein induced MAGE-A4-specific T cells from peripheral blood mononuclear cells of healthy donors...
March 2018: Experimental and Therapeutic Medicine
Seungwoo Kim, Hyosoon Cheon, Sam-Moon Kim, Young-Youl Kim
Background: Previous studies indicated that cadmium (Cd) increases PI3-kinase/Akt phosphorylation, resulting in an alteration in GSK-3β activity. However, the mechanism of Cd-induced endoplasmic reticulum (ER) stress in neuronal cells has yet to be studied in needs further elucidation. We examined the role of GSK-3β in Cd-induced neuronal cell death and the related downstream signaling pathways. Methods: SH-SY5Y human neuroblastoma cells were treated with 10 or 20 μM BAPTA-AM and 1 μM wortmannin for 30 min and then incubated with 25 μM Cd for 12 h...
2018: Cellular & Molecular Biology Letters
Florencia Díaz-Viraqué, María Laura Chiribao, Andrea Trochine, Fabiola González-Herrera, Christian Castillo, Ana Liempi, Ulrike Kemmerling, Juan Diego Maya, Carlos Robello
The discovery that trypanosomatids, unicellular organisms of the order Kinetoplastida, are capable of synthesizing prostaglandins raised questions about the role of these molecules during parasitic infections. Multiple studies indicate that prostaglandins could be related to the infection processes and pathogenesis in trypanosomatids. This work aimed to unveil the role of the prostaglandin F2 α synthase Tc OYE in the establishment of Trypanosoma cruzi infection, the causative agent of Chagas disease. This chronic disease affects several million people in Latin America causing high morbidity and mortality...
2018: Frontiers in Immunology
Marjolein W J Wentink, Yvonne M Mueller, Virgil A S H Dalm, Gertjan J Driessen, P Martin van Hagen, Joris M van Montfrans, Mirjam van der Burg, Peter D Katsikis
Pathogenic gain-of-function mutations in the gene encoding phosphoinositide 3-kinase delta (PI3Kδ) cause activated PI3Kδ syndrome (APDS), a disease characterized by humoral immunodeficiency, lymphadenopathy, and an inability to control persistent viral infections including Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections. Understanding the mechanisms leading to impaired immune response is important to optimally treat APDS patients. Immunosenescence of CD8+ T cells was suggested to contribute to APDS pathogenesis...
2018: Frontiers in Immunology
Na Guo, Sheng Ye, Kui Zhang, Xiaoling Yu, Hongyong Cui, Xiangmin Yang, Peng Lin, Minghua Lv, Jinlin Miao, Yang Zhang, Qing Han, Rongguang Zhang, Zhinan Chen, Ping Zhu
The abnormal activation of CD4+ CD45RO+ memory T (Tm) cells plays an important role in the pathogenesis of rheumatoid arthritis (RA). Previous studies have shown that CD147 participates in T-cell activation. However, it remains unclear whether CD147 is involved in abnormal Tm-cell activation in RA patients. In this study, we demonstrated that CD147 was predominantly upregulated in Tm cells derived from RA patients. The anti-CD147 mAb 5A12 specifically inhibited Tm-cell activation and proliferation and further restrained osteoclastogenesis...
March 21, 2018: Cellular & Molecular Immunology
Laura Tiberio, Annalisa Del Prete, Tiziana Schioppa, Francesca Sozio, Daniela Bosisio, Silvano Sozzani
Dendritic cells (DCs) are professional antigen-presenting cells responsible for the activation of specific T-cell responses and for the development of immune tolerance. Immature DCs reside in peripheral tissues and specialize in antigen capture, whereas mature DCs reside mostly in the secondary lymphoid organs where they act as antigen-presenting cells. The correct localization of DCs is strictly regulated by a large variety of chemotactic and nonchemotactic signals that include bacterial products, DAMPs (danger-associated molecular patterns), complement proteins, lipids, and chemokines...
March 21, 2018: Cellular & Molecular Immunology
Máira Tereza Talma Chírico, Frank Silva Bezerra, Mariana Reis Guedes, Ana Beatriz Souza, Fernanda Cacilda Silva, Glenda Campos, Sylvana Rendeiro de Noronha, Laura Batista Tavares Mesquita, Thayane Oliveira Reis, Silvia Dantas Cangussú, Deoclécio Alves Chianca-Jr, Rodrigo Cunha de Menezes
Smokers, who generally present with lung damage, are more anxious than non-smokers and have an associated augmented risk of panic. Considering that lung damage signals specific neural pathways that are related to affective responses, the aim of the present study was to evaluate the influence of pulmonary injury on anxiety and panic-like behaviours in animals exposed to cigarette smoke with and without tobacco. Male Wistar rats were divided into the following groups: a control group (CG); a regular cigarette group (RC); and a tobacco-free cigarette (TFC) group...
March 21, 2018: Scientific Reports
Luciane M Silva, Damon T Jacobs, Bailey A Allard, Timothy A Fields, Madhulika Sharma, Darren P Wallace, Pamela V Tran
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is caused by mutation of PKD1 or PKD2, which encode polycystin 1 and 2, respectively. The polycystins localize to primary cilia and the functional loss of the polycystin complex leads to the formation and progressive growth of fluid-filled cysts in the kidney. The pathogenesis of ADPKD is complex and molecular mechanisms connecting ciliary dysfunction to renal cystogenesis are unclear. Primary cilia mediate Hedgehog signaling, which modulates cell proliferation and differentiation in a tissue-dependent manner...
March 21, 2018: Scientific Reports
Nassima Chouaki-Benmansour, Kilian Ruminski, Anne-Marie Sartre, Marie-Claire Phelipot, Audrey Salles, Elise Bergot, Ambroise Wu, Gaëtan Chicanne, Mathieu Fallet, Sophie Brustlein, Cyrille Billaudeau, Anthony Formisano, Sébastien Mailfert, Bernard Payrastre, Didier Marguet, Sophie Brasselet, Yannick Hamon, Hai-Tao He
Phosphoinositides (PIs) play important roles in numerous membrane-based cellular activities. However, their involvement in the mechanism of T cell receptor (TCR) signal transduction across the plasma membrane (PM) is poorly defined. Here, we investigate their role, and in particular that of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] in TCR PM dynamics and activity in a mouse T-cell hybridoma upon ectopic expression of a PM-localized inositol polyphosphate-5-phosphatase (Inp54p). We observed that dephosphorylation of PI(4,5)P2 by the phosphatase increased the TCR/CD3 complex PM lateral mobility prior stimulation...
March 21, 2018: Scientific Reports
Jin-Yu Yang, Xiang-Yu Deng, Yi-Sheng Li, Xian-Cai Ma, Jian-Xiong Feng, Bing Yu, Yang Chen, Yi-Ling Luo, Xi Wang, Mei-Ling Chen, Zhi-Xin Fang, Fu-Xiang Zheng, Yi-Ping Li, Qian Zhong, Tie-Bang Kang, Li-Bing Song, Rui-Hua Xu, Mu-Sheng Zeng, Wei Chen, Hui Zhang, Wei Xie, Song Gao
Cleavage of transfer (t)RNA and ribosomal (r)RNA are critical and conserved steps of translational control for cells to overcome varied environmental stresses. However, enzymes that are responsible for this event have not been fully identified in high eukaryotes. Here, we report a mammalian tRNA/rRNA-targeting endoribonuclease: SLFN13, a member of the Schlafen family. Structural study reveals a unique pseudo-dimeric U-pillow-shaped architecture of the SLFN13 N'-domain that may clamp base-paired RNAs. SLFN13 is able to digest tRNAs and rRNAs in vitro, and the endonucleolytic cleavage dissevers 11 nucleotides from the 3'-terminus of tRNA at the acceptor stem...
March 21, 2018: Nature Communications
Frank Fasbender, Carsten Watzl
The use of impedance-based label free cell analysis is increasingly popular and has many different applications. Here, we report that a real-time cell analyzer (RTCA) can be used to study the stimulation of Natural Killer (NK) cells. Engagement of NK cells via plate-bound antibodies directed against different activating surface receptors could be measured in real time using the label-free detection of impedance. The change in impedance was dependent on early signal transduction events in the NK cells as it was blocked by inhibitors of Src-family kinases and by inhibiting actin polymerization...
March 21, 2018: Scientific Reports
Jason J Gokey, Anusha Sridharan, Yan Xu, Jenna Green, Gianni Carraro, Barry R Stripp, Anne-Karina T Perl, Jeffrey A Whitsett
Hippo/YAP signaling plays pleiotropic roles in the regulation of cell proliferation and differentiation during organogenesis and tissue repair. Herein we demonstrate increased YAP activity in respiratory epithelial cells in lungs of patients with idiopathic pulmonary fibrosis (IPF), a common, lethal form of interstitial lung disease (ILD). Immunofluorescence staining in IPF epithelial cells demonstrated increased nuclear YAP and loss of MST1/2. Bioinformatic analyses of epithelial cell RNA profiles predicted increased activity of YAP and increased canonical mTOR/PI3K/AKT signaling in IPF...
March 22, 2018: JCI Insight
Ciriana Orabona, Giada Mondanelli, Maria T Pallotta, Agostinho Carvalho, Elisa Albini, Francesca Fallarino, Carmine Vacca, Claudia Volpi, Maria L Belladonna, Maria G Berioli, Giulia Ceccarini, Susanna Mr Esposito, Raffaella Scattoni, Alberto Verrotti, Alessandra Ferretti, Giovanni De Giorgi, Sonia Toni, Marco Cappa, Maria C Matteoli, Roberta Bianchi, Davide Matino, Alberta Iacono, Matteo Puccetti, Cristina Cunha, Silvio Bicciato, Cinzia Antognelli, Vincenzo N Talesa, Lucienne Chatenoud, Dietmar Fuchs, Luc Pilotte, Benoît Van den Eynde, Manuel C Lemos, Luigina Romani, Paolo Puccetti, Ursula Grohmann
A defect in indoleamine 2,3-dioxygenase 1 (IDO1), which is responsible for immunoregulatory tryptophan catabolism, impairs development of immune tolerance to autoantigens in NOD mice, a model for human autoimmune type 1 diabetes (T1D). Whether IDO1 function is also defective in T1D is still unknown. We investigated IDO1 function in sera and peripheral blood mononuclear cells (PBMCs) from children with T1D and matched controls. These children were further included in a discovery study to identify SNPs in IDO1 that might modify the risk of T1D...
March 22, 2018: JCI Insight
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