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https://www.readbyqxmd.com/read/28635957/itk-signalling-via-the-ras-irf4-pathway-regulates-the-development-and-function-of-tr1-cells
#1
Weishan Huang, Sabrina Solouki, Nicholas Koylass, Song-Guo Zheng, Avery August
Type 1 regulatory T (Tr1) cells differentiate in response to signals engaging the T cell receptor (TCR), express high levels of the immunosuppressive cytokine IL-10, but not Foxp3, and can suppress inflammation and promote immune tolerance. Here we show that ITK, an important modulator of TCR signalling, is required for the TCR-induced development of Tr1 cells in various organs, and in the mucosal system during parasitic and viral infections. ITK kinase activity is required for mouse and human Tr1 cell differentiation...
June 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28631311/the-il-10-stat3-axis-contributions-to-immune-tolerance-by-thymus-and-peripherally-derived-regulatory-t-cells
#2
REVIEW
Klaus G Schmetterer, Winfried F Pickl
The signal transducer and activator of transcription (STAT) proteins are important mediators for the integration of extrinsic signals provided by cytokines and hormones and thereby adapt cellular processes to their surroundings. In the past decade, the involvement of STAT3 in the regulation of T-cell responses has become a topic of increasing interest. STAT3 is activated in response to multiple cytokines, many of which have been shown to influence T-cell responses. Interestingly, many of these factors have been described with apparent opposing roles, such as the highly pro-inflammatory potency of IL-6 and the anti-inflammatory properties of IL-10, thus raising the possibility that STAT3 signaling may fulfill diverse roles in CD4(+) T-cells...
June 20, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28631015/ask-yeast-how-to-burn-your-fats-lessons-learned-from-the-metabolic-adaptation-to-salt-stress
#3
REVIEW
Amparo Pascual-Ahuir, Sara Manzanares-Estreder, Alba Timón-Gómez, Markus Proft
Here, we review and update the recent advances in the metabolic control during the adaptive response of budding yeast to hyperosmotic and salt stress, which is one of the best understood signaling events at the molecular level. This environmental stress can be easily applied and hence has been exploited in the past to generate an impressively detailed and comprehensive model of cellular adaptation. It is clear now that this stress modulates a great number of different physiological functions of the cell, which altogether contribute to cellular survival and adaptation...
June 19, 2017: Current Genetics
https://www.readbyqxmd.com/read/28630419/iscador-qu-inhibits-doxorubicin-induced-senescence-of-mcf7-cells
#4
T Srdic-Rajic, J F Santibañez, K Kanjer, N Tisma-Miletic, M Cavic, D Galun, M Jevric, N Kardum, A Konic-Ristic, T Zoranovic
Chemotherapy in patients with inoperable or advanced breast cancer inevitably results in low-dose exposure of tumor-cell subset and senescence. Metabolically active senescent cells secrete multiple tumor promoting factors making their elimination a therapeutic priority. Viscum album is one of the most widely used alternative anti-cancer medicines facilitating chemotherapy tolerance of breast cancer patients. The aim of this study was to model and investigate how Viscum album extracts execute additive anti-tumor activity with low-dose Dox using ER + MCF7 breast cancer cells...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28630103/up-regulation-of-ep2-and-ep3-receptors-in-human-tolerogenic-dendritic-cells-boost-the-immunosuppressive-activity-of-pge2
#5
Georgina Flórez-Grau, Raquel Cabezón, Kyra J E Borgman, Carolina España, Juan Jose Lozano, Maria F Garcia-Parajo, Daniel Benítez-Ribas
Dendritic cells (DCs) are APCs essential in regulating the immune response. PGE2, produced during inflammation, has a pivotal role in the maturation of DCs and, therefore, is vital for the immune response. The large variety of biologic functions governed by PGE2 is mediated by its signaling through 4 distinct E-type prostanoid (EP) receptors. Immunogenic DCs express EP2 and EP4, which mediate the PGE2 signaling. However, the expression and function of EP receptors in human tolerogenic DCs (tol-DCs), which present an inhibitory phenotype, have not yet, to our knowledge, been assessed...
June 19, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28630077/what-are-the-primary-limitations-in-b-cell-affinity-maturation-and-how-much-affinity-maturation-can-we-drive-with-vaccination-breaking-through-immunity-s-glass-ceiling
#6
Garnett Kelsoe, Barton F Haynes
A key goal of HIV-1 vaccine development is the induction of broadly neutralizing antibodies (bnAbs) targeted to the vulnerable regions of the HIV envelope. BnAbs develop over time in ∼50% of HIV-1-infected individuals. However, to date, no vaccines have induced bnAbs and few or none of these vaccine-elicited HIV-1 antibodies carry the high frequencies of V(D)J mutations characteristic of bnAbs. Do the high frequencies of mutations characteristic of naturally induced bnAbs represent a fundamental barrier to the induction of bnAbs by vaccines? Recent studies suggest that high frequencies of V(D)J mutations can be achieved by serial vaccination strategies...
June 19, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28630062/the-transcription-factor-nfat1-participates-in-the-induction-of-cd4-t-cell-functional-exhaustion-during-plasmodium-yoelii-infection
#7
Rachel Y Ames, Li-Min Ting, Inessa Gendlina, Kami Kim, Fernando Macian
Repeated stimulation of T cells that occurs in the context of chronic infection results in progressively reduced responsiveness of T cells to pathogen-derived antigens. This phenotype, known as T cell exhaustion, occurs during chronic infections caused by a variety of pathogens, from persistent viruses to parasites. Unlike the memory cells that typically form after successful pathogen clearance following an acute infection, exhausted T cells secrete lower levels of effector cytokines, proliferate less in response to cognate antigen, and up-regulate cell-surface inhibitory molecules such as PD-1 and LAG-3...
June 19, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28628673/multiple-tolerance-defects-contribute-to-the-breach-of-b-cell-tolerance-in-new-zealand-black-chromosome-1-congenic-mice
#8
Nan-Hua Chang, Kieran P Manion, Christina Loh, Evelyn Pau, Yuriy Baglaenko, Joan E Wither
Lupus is characterized by a loss of B cell tolerance leading to autoantibody production. In this study, we explored the mechanisms underlying this loss of tolerance using B6 congenic mice with an interval from New Zealand Black chromosome 1 (denoted c1(96-100)) sufficient for anti-nuclear antibody production. Transgenes for soluble hen egg white lysozyme (sHEL) and anti-HEL immunoglobulin were crossed onto this background and various tolerance mechanisms examined. We found that c1(96-100) mice produced increased levels of IgM and IgG anti-HEL antibodies compared to B6 mice and had higher proportions of germinal center B cells and long-lived plasma cells, suggesting a germinal center-dependent breach of B cell anergy...
2017: PloS One
https://www.readbyqxmd.com/read/28624683/drought-responsive-micrornas-in-two-barley-cultivars-differing-in-their-level-of-sensitivity-to-drought-stress
#9
Ehsan Mohseni Fard, Behnam Bakhshi, Reza Keshavarznia, Nava Nikpay, Maryam Shahbazi, Ghasem Hosseini Salekdeh
MicroRNAs (miRNAs) are known to be involved in the regulation of gene expression, including that of genes involved in the response to stress. Here, a comparison has been drawn between the miRNA profiles of a drought susceptible, 'Morocco 9-75', and a drought tolerant, 'Yousef', barley cultivars. Leaf water content, shoot dry matter and chlorophyll content decreased in 'Morocco 9-75' more considerably compared with 'Yousef' under drought stress. Furthermore, lower stomatal conductance and higher leaf temperature were observed in 'Morocco 9-75' compared with 'Yousef'...
June 7, 2017: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/28623375/skin-immunity
#10
REVIEW
Agata Matejuk
Skin is the largest organ of the body with a complex network of multitude of cell types that perform plastic and dynamic cellular communication to maintain several vital processes such as inflammation, immune response including induction of tolerance and disease prevention, wound healing, and angiogenesis. Of paramount importance are immunological functions of the skin that protect from harmful exposure coming from external and internal environments. Awareness of skin immunity can provide a better comprehension of inflammation, autoimmunity, cancer, graft-versus-host disease, vaccination, and immunotherapy approaches...
June 16, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28623353/the-efficacy-and-toxicities-of-intensive-induction-chemotherapy-followed-by-concurrent-chemoradiotherapy-in-nasopharyngeal-carcinoma-patients-with-n3-disease
#11
Yingying Zhang, Mingqiu Chen, Cheng Chen, Lin Kong, Jiade J Lu, Benhua Xu
To assess the feasibility, efficacy and safety of 4 cycles of induction chemotherapy (ICT) followed by concurrent chemoradiotherapy (CRT) in nasopharyngeal carcinoma (NPC) patients with N3 disease. ICT consisting of paclitaxel (135 mg/m(2)) and nedaplatin (80 mg/m(2)) given every 3 weeks for 4 cycles followed by cisplatin-based CRT was planned. 22 patients completed 4 cycles of TP regimen ICT and the CRT according to the protocol. After 4 cycles of ICT, the ORR of the primary site was 100% (CR 22.7%, PR 77...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28622511/metabolic-adaptation-establishes-disease-tolerance-to-sepsis
#12
Sebastian Weis, Ana Rita Carlos, Maria Raquel Moita, Sumnima Singh, Birte Blankenhaus, Silvia Cardoso, Rasmus Larsen, Sofia Rebelo, Sascha Schäuble, Laura Del Barrio, Gilles Mithieux, Fabienne Rajas, Sandro Lindig, Michael Bauer, Miguel P Soares
Sepsis is an often lethal syndrome resulting from maladaptive immune and metabolic responses to infection, compromising host homeostasis. Disease tolerance is a defense strategy against infection that preserves host homeostasis without exerting a direct negative impact on pathogens. Here, we demonstrate that induction of the iron-sequestering ferritin H chain (FTH) in response to polymicrobial infections is critical to establish disease tolerance to sepsis. The protective effect of FTH is exerted via a mechanism that counters iron-driven oxidative inhibition of the liver glucose-6-phosphatase (G6Pase), and in doing so, sustains endogenous glucose production via liver gluconeogenesis...
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28615301/irf4-dependent-cd103-cd11b-dendritic-cells-and-the-intestinal-microbiome-regulate-monocyte-and-macrophage-activation-and-intestinal-peristalsis-in-postoperative-ileus
#13
Judith-Mira Pohl, Sebastian Gutweiler, Stephanie Thiebes, Julia K Volke, Ludger Klein-Hitpass, Denise Zwanziger, Matthias Gunzer, Steffen Jung, William W Agace, Daniel Robert Engel, Christian Kurts
OBJECTIVE: Postoperative ileus (POI), the most frequent complication after intestinal surgery, depends on dendritic cells (DCs) and macrophages. Here, we have investigated the mechanism that activates these cells and the contribution of the intestinal microbiota for POI induction. DESIGN: POI was induced by manipulating the intestine of mice, which selectively lack DCs, monocytes or macrophages. The disease severity in the small and large intestine was analysed by determining the distribution of orally applied fluorescein isothiocyanate-dextran and by measuring the excretion time of a retrogradely inserted glass ball...
June 14, 2017: Gut
https://www.readbyqxmd.com/read/28614294/human-fetal-dendritic-cells-promote-prenatal-t-cell-immune-suppression-through-arginase-2
#14
Naomi McGovern, Amanda Shin, Gillian Low, Donovan Low, Kaibo Duan, Leong Jing Yao, Rasha Msallam, Ivy Low, Nurhidaya Binte Shadan, Hermi R Sumatoh, Erin Soon, Josephine Lum, Esther Mok, Sandra Hubert, Peter See, Edwin Huang Kunxiang, Yie Hou Lee, Baptiste Janela, Mahesh Choolani, Citra Nurfarah Zaini Mattar, Yiping Fan, Tony Kiat Hon Lim, Dedrick Kok Hong, Ker-Kan Tan, John Kit Chung Tam, Christopher Schuster, Adelheid Elbe-Bürger, Xiao-Nong Wang, Venetia Bigley, Matthew Collin, Muzlifah Haniffa, Andreas Schlitzer, Michael Poidinger, Salvatore Albani, Anis Larbi, Evan W Newell, Jerry Kok Yen Chan, Florent Ginhoux
During gestation the developing human fetus is exposed to a diverse range of potentially immune-stimulatory molecules including semi-allogeneic antigens from maternal cells, substances from ingested amniotic fluid, food antigens, and microbes. Yet the capacity of the fetal immune system, including antigen-presenting cells, to detect and respond to such stimuli remains unclear. In particular, dendritic cells, which are crucial for effective immunity and tolerance, remain poorly characterized in the developing fetus...
June 14, 2017: Nature
https://www.readbyqxmd.com/read/28612430/igg-subclasses-of-fviii-inhibitors-in-an-argentine-cohort-of-severe-hemophilia-a-patients-analysis-by-flow-cytometry
#15
M B Irigoyen, L Primiani, M Felippo, M Candela, M M E de Bracco, N V Galassi
INTRODUCTION: FVIII inhibitors consist of a polyclonal population of antibodies. Previous studies have demonstrated different distribution of IgG subclasses. IgG4 was associated to high level of FVIII inhibitors and failure of immune tolerance induction (ITI) treatment. This study monitored the relative distribution of IgG subclasses of anti-FVIII in patients with severe hemophilia A (SHA). METHODS: Anti-FVIII antibodies were measured employing an immunomethod, developed in our laboratory, that combines flow cytometry (FC) with microspheres coupled (FVIII-m) or not (Control-m) to FVIII...
June 14, 2017: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/28611770/relevance-of-cd6-mediated-interactions-in-the-regulation-of-peripheral-t-cell-responses-and-tolerance
#16
Marta Consuegra-Fernández, Mario Martínez-Florensa, Fernando Aranda, José de Salort, Noelia Armiger-Borràs, Teresa Lozano, Noelia Casares, Juan José Lasarte, Pablo Engel, Francisco Lozano
The CD6 lymphocyte receptor has been involved in the pathophysiology of different autoimmune disorders and is now considered a feasible target for their treatment. In vitro data show the relevance of CD6 in the stabilization of adhesive contacts between T-cell and antigen-presenting cells, and the modulation of T-cell receptor signals. However, the in vivo consequences of such a function are yet undisclosed due to the lack of suitable genetically modified animal models. Here, the in vitro and in vivo challenge of CD6-deficient (CD6(-/-)) cells with allogeneic cells was used as an approach to explore the role of CD6 in immune responses under relative physiological stimulatory conditions...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28611473/apc-targeted-proinsulin-expression-inactivates-insulin-specific-memory-cd8-t-cells-in-nod-mice
#17
Peta Ls Reeves, Rajeev Rudraraju, Xiao Liu, F Susan Wong, Emma E Hamilton-Williams, Raymond J Steptoe
Type 1 diabetes (T1D) results from T-cell mediated autoimmune destruction of pancreatic β cells. Effector T-cell responses emerge early in disease development and expand as disease progresses. Following β cell destruction, a long-lived T-cell memory is generated that represents a barrier to islet transplantation and other cellular insulin-replacement therapies. Development of effective immunotherapies that control or ablate β cell destructive effector and memory T cell responses has the potential to prevent disease progression and recurrence...
June 14, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28609207/protection-of-lipopolysaccharide-lps-preconditioning-against-endotoxin-induced-uveitis-eiu-in-rats-is-associated-with-overexpression-of-interleukin-1-receptor-associated-kinase-m-irak-m
#18
Shuo Yu, Xinli Liu, Nan Zhang, Shuo Yang, Cui Mao, Shilan Feng, Hong Lu
PURPOSE: To investigate the protective effect of LPS preconditioning against EIU in rats. METHODS: EIU in Wistar rats was developed by subcutaneous injection of LPS (200 μg). Lower dose of LPS (0.1 mg/kg, intraperitoneally) or its carrier was injected daily for five days before EIU induction. Twenty-four hours after EIU, eyes were examined and then enucleated. The degree of inflammatory reaction was determined by routine histological examinations. Real-time RT-PCR and Western blot were used to determine the activation of NF-kB and expression of IRAK-1, IRAK-4, and IRAK-M Results: Repeated pre-administration of LPS induced a significant reduction in ocular inflammation and the expression of NF-κb p65 in neurons...
June 13, 2017: Ocular Immunology and Inflammation
https://www.readbyqxmd.com/read/28609185/discovery-and-preclinical-development-of-netarsudil-a-novel-ocular-hypotensive-agent-for-the-treatment-of-glaucoma
#19
Cheng-Wen Lin, Bryan Sherman, Lori A Moore, Carmen L Laethem, Da-Wen Lu, Padmanabhan P Pattabiraman, Ponugoti Vasantha Rao, Mitchell A deLong, Casey C Kopczynski
PURPOSE: Rho-associated protein kinase (ROCK) inhibitors lower intraocular pressure (IOP) by increasing aqueous outflow through the trabecular meshwork (TM). The preclinical characterization of netarsudil, a new ROCK/norepinephrine transporter (NET) inhibitor currently in clinical development, is presented herein. METHODS: The kinase inhibitory activity of netarsudil was compared to its esterase metabolite, netarsudil-M1, and 3 other ROCK inhibitors using a commercially available kinase assay kit...
June 13, 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28608279/the-recombinant-fusion-protein-of-cholera-toxin-b-and-neutrophil-activating-protein-expressed-on-bacillus-subtilis-spore-surface-suppresses-allergic-inflammation-in-mice
#20
Hui Dong, Yanmei Huang, Shuwen Yao, Bingshao Liang, Yan Long, Yongqiang Xie, Jialiang Mai, Sitang Gong, Zhenwen Zhou
The neutrophil-activating protein of Helicobacter pylori (HP-NAP) has been identified as a modulator with anti-Th2 inflammation activity, and cholera toxin B (CTB) is a mucosal adjuvant that can also induce antigen tolerance. In this study, we constructed a CTB-NAP fusion protein on the surface of Bacillus subtilis spore and evaluate the efficiency of oral administration of the recombinant CTB-NAP spores in preventing asthma in mice. Oral administration of recombinant CTB or CTB-NAP spores significantly decreased serum ovalbumin (OVA)-specific IgE (p < 0...
June 12, 2017: Applied Microbiology and Biotechnology
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