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https://www.readbyqxmd.com/read/29351392/young-mice-expel-the-tapeworm-hymenolepis-diminuta-and-are-protected-from-colitis-by-triggering-a-memory-response-with-worm-antigen
#1
Toshio Arai, Fernando Lopes, Adam Shute, Arthur Wang, Derek M McKay
Infection with helminth parasites reduces the severity of concomitant inflammatory disease in adult mice. There is an alarming increase of IBD in children. It is important to determine if helminth therapy would be of value in pediatric IBD, and if triggering immunological memory to the worm would be anti-colitic. Three-week (young) and eight-week (adult) old Balb/c mice were infected with H. diminuta, and infectivity and T helper (TH)-2 immunity assessed. Other mice received H. diminuta {plus minus} a crude worm extract (HdE) 28-42 days post-infection (dpi) {plus minus} dinitrobenzene sulphonic acid (DNBS; 1...
January 4, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29346301/braf-and-mek-inhibitors-influence-the-function-of-reprogrammed-t-cells-consequences-for-adoptive-t-cell-therapy
#2
Jan Dörrie, Lek Babalija, Stefanie Hoyer, Kerstin F Gerer, Gerold Schuler, Lucie Heinzerling, Niels Schaft
BRAF and MEK inhibitors (BRAFi/MEKi), the standard treatment for patients with BRAFV600 mutated melanoma, are currently explored in combination with various immunotherapies, notably checkpoint inhibitors and adoptive transfer of receptor-transfected T cells. Since two BRAFi/MEKi combinations with similar efficacy are approved, potential differences in their effects on immune cells would enable a rational choice for triple therapies. Therefore, we characterized the influence of the clinically approved BRAFi/MEKi combinations dabrafenib (Dabra) and trametinib (Tram) vs...
January 18, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29345354/lack-of-functional-selectin-ligand-interactions-enhances-innate-immune-resistance-to-systemic-listeria-monocytogenes-infection
#3
Gerard Agbayani, Komal Gurnani, Ahmed Zafer, Subash Sad, Lakshmi Krishnan
Selectin-ligand interactions are important for leukocyte homing and functionality. The roles of selectin-ligand interactions in modulating immunity to intracellular infections are not completely understood. Mice lacking the expression of fucosyltransferase-IV and -VII (Fucosyltransferase-IV and -VII double knockout, FtDKO) exhibit deficient functionality of selectin-ligand interactions. We addressed the kinetics of infection and immunity to Listeria monocytogenes (LM), an intracellular pathogen, in FtDKO mice...
December 27, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29345336/%C3%AE-%C3%AE-cells-and-tumor-microenvironment-a-helpful-or-a-dangerous-liason
#4
REVIEW
Elena Lo Presti, Roberto Di Mitri, Gabriele Pizzolato, Filippo Mocciaro, Francesco Dieli, Serena Meraviglia
γδ T cells are a subset of T lymphocytes that have been implicated in immunosurveillance against infections and tumors. γδ T cells are endowed with antitumor activities, and hence several γδ T cell-based small-scale clinical trials have been conducted either by in vivo activation by intravenous administration of aminobiphosphonates or by adoptive transfer of in vitro expanded γδ T cells. Although both these strategies have yielded promising results, there are a number of limitations associated with each of them which, if overcome may help to further improve efficacy...
December 14, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29345057/sodium-chloride-inhibits-ifn-%C3%AE-%C3%A2-but-not-il-4-production-by-invariant-nkt-cells
#5
Dongjin Jeong, Hye Young Kim, Doo Hyun Chung
Invariant NKT (iNKT) cells are a distinct subset of T cells that exert Janus-like functions in vivo by producing IFN-γ and IL-4. Sodium chloride modulates the functions of various immune cells, including conventional CD4+ T cells and macrophages. However, it is not known whether sodium chloride affects iNKT cell function, so we addressed this issue. Sodium chloride inhibited IFN-γ, but not IL-4, production by iNKT cells upon TCR or TCR-independent (IL-12 and IL-18) stimulation in a dose-dependent manner. Consistently, sodium chloride reduced the expression level of tbx21, but not gata-3, in iNKT cells stimulated with TCR engagement or IL-12 + IL-18...
January 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29344311/gilz-activin-a-as-a-novel-signaling-axis-orchestrating-mesenchymal-stem-cell-and-th17-cell-interplay
#6
Patricia Luz-Crawford, Gabriel Espinosa-Carrasco, Natacha Ipseiz, Rafael Contreras, Gautier Tejedor, Daniel A Medina, Ana-Maria Vega-Letter, Devi Ngo, Eric F Morand, Jérôme Pène, Javier Hernandez, Christian Jorgensen, Farida Djouad
Mesenchymal stem cells (MSC) are highly immunosuppressive cells able to reduce chronic inflammation through the active release of mediators. Recently, we showed that glucocorticoid-induced leucine zipper (Gilz) expression by MSC is involved in their therapeutic effect by promoting the generation of regulatory T cells. However, the mechanisms underlying this pivotal role of Gilz remain elusive. Methods and Results In this study, we have uncovered evidence that Gilz modulates the phenotype and function of Th1 and Th17 cells likely by upregulating the level of Activin A and NO2 secreted by MSC...
2018: Theranostics
https://www.readbyqxmd.com/read/29342200/inhibiting-tgf-beta-signaling-preserves-the-function-of-highly-activated-in-vitro-expanded-natural-killer-cells-in-aml-and-colon-cancer-models
#7
Folashade Otegbeye, Evelyn Ojo, Stephen Moreton, Nathan Mackowski, Dean A Lee, Marcos de Lima, David N Wald
Natural killer cells harnessed from healthy individuals can be expanded ex vivo using various platforms to produce large doses for adoptive transfer into cancer patients. During such expansion, NK cells are increasingly activated and more efficient at killing cancer cells. Adoptive transfer however introduces these activated cells into a highly immunosuppressive tumor microenvironment mediated in part by excessive transforming growth factor beta (TGF-beta) from both cancer cells and their surrounding stroma...
2018: PloS One
https://www.readbyqxmd.com/read/29340102/the-impact-of-antibiotic-usage-on-the-efficacy-of-chemoimmunotherapy-is-contingent-on-the-source-of-tumor-reactive-t-cells
#8
Michal P Kuczma, Zhi-Chun Ding, Tao Li, Tsadik Habtetsion, Tingting Chen, Zhonglin Hao, Locke Bryan, Nagendra Singh, James N Kochenderfer, Gang Zhou
In recent years the combined use of chemotherapy and immunotherapy, collectively termed chemoimmunotherapy, has emerged as a promising treatment option for patients with cancer. Antibiotics are commonly used to reduce infection-related complications in patients undergoing chemotherapy. Intriguingly, accumulating evidence has implicated gut microbiota as a critical determinant of host antitumor immune responses, raising the question as to whether the use of broad-spectrum antibiotics would invariably diminish tumor response to chemoimmunotherapies...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339772/foxo1-promotes-th9-cell-differentiation-and-airway-allergy
#9
Thomas S Buttrick, Wei Wang, Christina Yung, Kenneth G Trieu, Kruti Patel, Samia J Khoury, Xingbin Ai, Wassim Elyaman
T helper 9 (Th9) cells are effector CD4+ T cells that are characterized by the production of interleukin-9 (IL-9) and have been associated with allergic responses. Here, we found that the expression of the transcription factor forkhead box O1 (Foxo1) was induced in Th9 and Foxo1 plays a crucial role in the differentiation of Th9 cells. Pharmacological inhibition of Foxo1 or genetic disruption of Foxo1 in CD4+ T cells caused a reduction in IL-9 expression while upregulating IL-17A and IFNγ production. Furthermore, chromatin immunoprecipitation (ChIP) followed by luciferase assays revealed direct binding of Foxo1 to both the Il9 and Irf4 promoters and induces their transactivation...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29339767/regulatory-t-cells-trigger-effector-t-cell-dna-damage-and-senescence-caused-by-metabolic-competition
#10
Xia Liu, Wei Mo, Jian Ye, Lingyun Li, Yanping Zhang, Eddy C Hsueh, Daniel F Hoft, Guangyong Peng
Defining the suppressive mechanisms used by regulatory T (Treg) cells is critical for the development of effective strategies for treating tumors and chronic infections. The molecular processes that occur in responder T cells that are suppressed by Treg cells are unclear. Here we show that human Treg cells initiate DNA damage in effector T cells caused by metabolic competition during cross-talk, resulting in senescence and functional changes that are molecularly distinct from anergy and exhaustion. ERK1/2 and p38 signaling cooperate with STAT1 and STAT3 to control Treg-induced effector T-cell senescence...
January 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29339208/targeted-shrna-loaded-liposome-complex-combined-with-focused-ultrasound-for-blood-brain-barrier-disruption-and-suppressing-glioma-growth
#11
Guanjian Zhao, Qin Huang, Feng Wang, Xiang Zhang, Jiangang Hu, Ying Tan, Ning Huang, Zhigang Wang, Zhibiao Wang, Yuan Cheng
Our previous studies have demonstrated that focused ultrasound (FUS) combined with DNA-loaded microbubbles (MBs) can induce noninvasive, reversible, local disruption of the blood brain barrier (BBB) and enable targeted exogenous gene transfer into the central nervous system. However, due to low gene loading or the absence of positive targeting, to date, there has been no therapeutic effect of MBs combined with FUS in tumor treatment. In the current study, we adopted a phospholipid complex that exhibited sufficient gene loading and peptide-mediated targeting to delay glioma growth...
January 12, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29338160/higher-activities-of-hepatic-versus-splenic-cd8-t-cells-in-responses-to-adoptive-t-cell-therapy-and-vaccination-of-b6-mice-with-mhc-class-1-binding-antigen
#12
Mohamed Labib Salem, Randa E El Naggar, Sabry A El Naggar, Maysa A Mobasher, Mohamed H Mahmoud, Gamal Badr
The liver has unique microenvironment which is known to induce tolerance of cytolytic CD8+ T cells to hepatic and extra hepatic antigens, resulting in persistence of infection of the liver by the hepatitis B and C viruses. However, under some conditions, functional immune responses can be elicited in the liver in particular to show preferential retention of activated CD8+ T cells. It is not clear whether this retention depends on the type of the exogenous immunostimulatory or the endogenous innate immune cells...
December 2017: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/29338084/importance-of-b-cells-to-development-of-tregs-and-prolongation-of-tissue-allograft-survival-in-recipients-receiving-autologous-bone-marrow-transplantation
#13
Reginald M Gorczynski, Kaveh Farrokhi, Christopher Gorczynski, Hassan Sadozai, Fang Zhu, Ismat Khatri
We previously showed that congenic bone marrow transplantation (BMTx) post myeloablation augmented tissue allograft survival in association with increased Tregs of both host and bone marrow donor origin. Regulatory B cells (Bregs) can also modulate T cell immunity and B cells may be implicated in the development of Tregs. Accordingly, we explored the effect of B cell depletion in vivo on augmented graft survival post BMTx. C57BL/6 mice received BALB/c skin allografts followed 7d later by myeloablation using cyclophosphamide and busulphan...
January 16, 2018: Immunology
https://www.readbyqxmd.com/read/29336483/glucose-metabolism-during-in-vitro-maturation-of-mouse-oocytes-an-study-using-rna-interference
#14
Hong-Li Xie, Shuai Zhu, Jie Zhang, Jing Wen, Hong-Jie Yuan, Liu-Zhu Pan, Ming-Jiu Luo, Jing-He Tan
In previous studies on glucose metabolism during in vitro maturation, intact cumulus-oocyte complexes (COCs) were treated with enzyme inhibitors/activators. Because inhibitors/activators may have non-specificity and/or toxicity, and culture of COCs cannot differentiate whether glucose metabolism of cumulus cells (CCs) or that of the oocyte supports oocyte maturation, results from the previous studies must be verified by silencing genes in either CCs or cumulus-denuded oocytes (DOs). In this study, RNAi was adopted to specify the effects of glucose metabolism in CCs or DOs on oocyte maturation...
January 16, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29335647/aged-polymorphonuclear-leukocytes-cause-fibrotic-interstitial-lung-disease-in-the-absence-of-regulation-by-b-cells
#15
Jung Hwan Kim, John Podstawka, Yuefei Lou, Lu Li, Esther K S Lee, Maziar Divangahi, Björn Petri, Frank R Jirik, Margaret M Kelly, Bryan G Yipp
Pulmonary immunity requires tight regulation, as interstitial inflammation can compromise gas exchange and lead to respiratory failure. Here we found a greater number of aged CD11bhiL-selectinloCXCR4+ polymorphonuclear leukocytes (PMNs) in lung vasculature than in the peripheral circulation. Using pulmonary intravital microscopy, we observed lung PMNs physically interacting with B cells via β2 integrins; this initiated neutrophil apoptosis, which led to macrophage-mediated clearance. Genetic deletion of B cells led to the accumulation of aged PMNs in the lungs without systemic inflammation, which caused pathological fibrotic interstitial lung disease that was attenuated by the adoptive transfer of B cells or depletion of PMNs...
January 15, 2018: Nature Immunology
https://www.readbyqxmd.com/read/29332826/a-robust-and-extendable-sheath-flow-interface-with-minimal-dead-volume-for-coupling-ce-with-esi-ms
#16
Pan Fang, Jian-Zhang Pan, Qun Fang
In this paper, we describe a robust sheath flow-based CE-MS interface with minimal interface dead volume based on an extended pattern. A 20µm i.d. × 90µm o.d. fused-silica capillary with a chemically-etched thin-wall tip (30µm o.d.) was used as the separation capillary as well as electrospray emitter, and a 200µm i.d. × 375µm o.d. capillary with a tapered tip (40µm o.d.) was used as the sheath flow capillary. An extendable sheath-flow interface mode was adopted by decreasing the thickness of separation capillary tip and extending the separation capillary tip out from the sheath flow capillary tip, and allowing the sheath flow to be transferred to the separation capillary tip along its outer surface, forming a surface sheath flow to mix with sample flow at the separation capillary tip...
April 1, 2018: Talanta
https://www.readbyqxmd.com/read/29332158/combined-sublethal-irradiation-and-agonist-anti-cd40-enhance-donor-t-cell-accumulation-and-control-of-autochthonous-murine-pancreatic-tumors
#17
Lindsay K Ward-Kavanagh, Kathleen M Kokolus, Timothy K Cooper, Aron E Lukacher, Todd D Schell
Tumor-reactive T lymphocytes can promote the regression of established tumors. However, their efficacy is often limited by immunosuppressive mechanisms that block T cell accumulation or function. ACT provides the opportunity to ameliorate immune suppression prior to transfer of tumor-reactive T cells to improve the therapeutic benefit. We evaluated the combination of lymphodepleting whole body irradiation (WBI) and agonist anti-CD40 (αCD40) antibody on control of established autochthonous murine neuroendocrine pancreatic tumors following the transfer of naïve tumor-specific CD8 T cells...
January 13, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29331106/kbtbd2-inhibits-the-cytotoxic-activity-of-immortalized-nk-cells-through-down-regulating-mtor-signaling-in-a-mouse-hepatocellular-carcinoma-model
#18
Kai Dai, Yabing Huang, Zubing Chen, Xiaomei Sun, Lihua Yang, Yingan Jiang
Natural killer cell (NK cell)-based immunotherapy is a promising therapeutic strategy for hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying the regulation of NK cell function in the tumor sites are not completely elucidated. In this study, we identified the enhanced expression of kelch repeat and BTB (POZ) domain containing 2 (Kbtbd2) in intratumoral NK cells in a mouse HCC implantation model as a negative regulator of NK cells. To investigate this interaction,, we used a Tet-on inducible expression system to control Kbtbd2 expression in an immortalized mouse NK cell line KIL C...
January 13, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29329051/non-genetic-engineering-of-cytotoxic-t-cells-to-target-il-4-receptor-enhances-tumor-homing-and-therapeutic-efficacy-against-melanoma
#19
Gowri Rangaswamy Gunassekaran, Chae-Moon Hong, Sri Murugan Poongkavithai Vadevoo, Lianhua Chi, Padmanaban Guruprasath, Byung-Cheol Ahn, Ha-Jeong Kim, Tae Heung Kang, Byungheon Lee
Adoptive transfer of cytotoxic T lymphocytes (CTLs) has been used as an immunotherapy in melanoma. However, the tumor homing and therapeutic efficacy of transferred CTLs against melanoma remain unsatisfactory. Interleukin-4 receptor (IL-4R) is commonly up-regulated in tumors including melanoma. Here, we studied whether IL-4R-targeted CTLs exhibit enhanced tumor homing and therapeutic efficacy against melanoma. CTLs isolated from mice bearing melanomas were non-genetically engineered with IL4RPep-1, an IL-4R-binding peptide, using a membrane anchor composed of dioleylphosphatidylethanolamine...
January 8, 2018: Biomaterials
https://www.readbyqxmd.com/read/29328912/bcg-educates-hematopoietic-stem-cells-to-generate-protective-innate-immunity-against-tuberculosis
#20
Eva Kaufmann, Joaquin Sanz, Jonathan L Dunn, Nargis Khan, Laura E Mendonça, Alain Pacis, Fanny Tzelepis, Erwan Pernet, Anne Dumaine, Jean-Christophe Grenier, Florence Mailhot-Léonard, Eisha Ahmed, Jad Belle, Rickvinder Besla, Bruce Mazer, Irah L King, Anastasia Nijnik, Clinton S Robbins, Luis B Barreiro, Maziar Divangahi
The dogma that adaptive immunity is the only arm of the immune response with memory capacity has been recently challenged by several studies demonstrating evidence for memory-like innate immune training. However, the underlying mechanisms and location for generating such innate memory responses in vivo remain unknown. Here, we show that access of Bacillus Calmette-Guérin (BCG) to the bone marrow (BM) changes the transcriptional landscape of hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs), leading to local cell expansion and enhanced myelopoiesis at the expense of lymphopoiesis...
January 11, 2018: Cell
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