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https://www.readbyqxmd.com/read/30022064/tbk-binding-protein-1-regulates-il-15-induced-autophagy-and-nkt-cell-survival
#1
Lele Zhu, Xiaoping Xie, Lingyun Zhang, Hui Wang, Zuliang Jie, Xiaofei Zhou, Jianhong Shi, Shuli Zhao, Boxiang Zhang, Xuhong Cheng, Shao-Cong Sun
The cytokine IL-15 mediates development and survival of immune cells, including natural killer T (NKT) cells, but the underlying mechanism of IL-15 function is incompletely understood. Here we show that IL-15 induces autophagy in NKT cells with a mechanism that involves a crucial signaling component, TBK-binding protein 1 (Tbkbp1). Tbkbp1 facilitates activation of the autophagy-initiating kinase Ulk1 through antagonizing the inhibitory action of mTORC1. This antagonization involves the recruitment of an mTORC1-opposing phosphatase to Ulk1...
July 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/30021579/anti-cancer-activity-of-angelica-gigas-by-increasing-immune-response-and-stimulating-natural-killer-and-natural-killer-t-cells
#2
Seo Hyun Kim, Sung Won Lee, Hyun Jung Park, Sang Hee Lee, Won Kyun Im, Young Dong Kim, Kyung Hee Kim, Sang Jae Park, Seokmann Hong, Sung Ho Jeon
BACKGROUND: The polysaccharide component of Angelica gigas induces immuno-stimulatory effects on innate immune cells. However, it is unclear whether A. gigas' adjuvant activity on the immune system can elicit anti-cancer responses. METHODS: A water-soluble immuno-stimulatory component of A. gigas was prepared. How this ISAg modulated the activation of innate immune cells such as dendritic cells (DCs) was examined. ISAg-induced cytotoxic activity via natural killer (NK) and NKT cells was also tested using a tumor-bearing mouse model...
July 18, 2018: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/30019146/naturally-produced-type-i-ifns-enhance-human-myeloid-dendritic-cell-maturation-and-il-12p70-production-and-mediate-elevated-effector-functions-in-innate-and-adaptive-immune-cells
#3
Annette E Sköld, Till S M Mathan, Jasper J P van Beek, Georgina Flórez-Grau, Michelle D van den Beukel, Simone P Sittig, Florian Wimmers, Ghaith Bakdash, Gerty Schreibelt, I Jolanda M de Vries
There has recently been a paradigm shift in the field of dendritic cell (DC)-based immunotherapy, where several clinical studies have confirmed the feasibility and advantageousness of using directly isolated human blood-derived DCs over in vitro differentiated subsets. There are two major DC subsets found in blood; plasmacytoid DCs (pDCs) and myeloid DCs (mDCs), and both have been tested clinically. CD1c+ mDCs are highly efficient antigen-presenting cells that have the ability to secrete IL-12p70, while pDCs are professional IFN-α-secreting cells that are shown to induce innate immune responses in melanoma patients...
July 13, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/30013034/activation-of-natural-killer-t-cells-contributes-to-triptolide-induced-liver-injury-in-mice
#4
Xin-Zhi Wang, Ru-Feng Xue, Shen-Ye Zhang, Ya-Ting Zheng, Lu-Yong Zhang, Zhen-Zhou Jiang
Triptolide (TP) is the main active ingredient of Tripterygium wilfordii Hook.f, which has attracted great interest due to its promising efficacy for autoimmune diseases and tumors. However, severe adverse reactions, especially hepatotoxicity, have restricted its approval in the market. In the present study we explored the role of hepatic natural killer T (NKT) cells in the pathogenesis of TP-induced liver injury in mice. TP (600 μg/kg/day, i.g.) was administered to female mice for 1, 3, or 5 days. We found that administration of TP dose-dependently induced hepatotoxicity, evidenced by the body weight reduction, elevated serum ALT and AST levels, as well as significant histopathological changes in the livers...
July 16, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/30012846/id3-restricts-%C3%AE-%C3%AE-nkt-cell-expansion-by-controlling-egr2-and-c-myc-activity
#5
Baojun Zhang, Anjun Jiao, Meifang Dai, David L Wiest, Yuan Zhuang
γδ NKT cells are neonatal-derived γδ T lymphocytes that are grouped together with invariant NKT cells based on their shared innate-like developmental program characterized by the transcription factor PLZF (promyelocytic leukemia zinc finger). Previous studies have demonstrated that the population size of γδ NKT cells is tightly controlled by Id3-mediated inhibition of E-protein activity in mice. However, how E proteins promote γδ NKT cell development and expansion remains to be determined. In this study, we report that the transcription factor Egr2, which also activates PLZF expression in invariant NKT cells, is essential for regulating γδ NKT cell expansion...
July 16, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30012672/activation-of-nkt-cells-in-an-anti-pd-1-resistant-tumor-model-enhances-anti-tumor-immunity-by-reinvigorating-exhausted-cd8-t-cells
#6
Eun-Ah Bae, Hyungseok Seo, Byung-Seok Kim, Jeongwon Choi, Insu Jeon, Kwang-Soo Shin, Choong-Hyun Koh, Boyeong Song, Il-Kyu Kim, Byung Soh Min, Yoon Dae Han, Sang Joon Shin, Chang-Yuil Kang
PD-1-based cancer immunotherapy is a successful example of immune checkpoint blockade that provides long-term durable therapeutic effects in cancer patients across a wide spectrum of cancer types. Accumulating evidence suggests that anti-PD-1 therapy enhances anti-tumor immunity by reversing the function of exhausted T cells in the tumor environment. However, the responsiveness rate of cancer patients to anti-PD-1 therapy remains low, providing an urgent need for optimization and improvement. In this study, we designed an anti-PD-1-resistant mouse tumor model and showed that unresponsiveness to anti-PD-1 is associated with a gradual increase in CD8 T cell exhaustion...
July 16, 2018: Cancer Research
https://www.readbyqxmd.com/read/30012191/immunosuppressive-property-of-submandibular-lymph-nodes-in-patients-with-head-and-neck-tumors-differential-distribution-of-regulatory-t-cells
#7
Daiju Sakurai, Ryosuke Uchida, Fumie Ihara, Naoki Kunii, Takuya Nakagawa, Hideaki Chazono, Toyoyuki Hanazawa, Shinichiro Motohashi, Yoshitaka Okamoto
OBJECTIVE: Different sensitizations and immune responses are thought to be induced in response to antigens at different mucosal sites between the oral floor and nose. The aim of this study was to investigate differences in the distributions of lymphocyte subsets in the submandibular (SM) and upper jugular (UJ) lymph nodes (LNs), which are supposed to be regional LNs of the oral floor and nasal mucosa, respectively. SMLNs and UJLNs were collected from patients with head and neck tumors who underwent surgical resection...
July 16, 2018: BMC Research Notes
https://www.readbyqxmd.com/read/30008645/presence-of-chlamydophila-pneumoniae-dna-in-blood-cells-is-a-frequent-event-in-patients-with-the-late-stage-of-primary-cutaneous-lymphomas-and-with-atopic-dermatitis
#8
Bogusław Nedoszytko, Piotr Wierzbicki, Leena Karenko, Agata Maciejewska-Radomska, Przemysław Stachewicz, Monika Zabłotna, Jolanta Gleń, Liisa Väkevä, Roman J Nowicki, Małgorzata Sokołowska-Wojdyło
Introduction: Microbial infection and associated super antigens have been implicated in the pathogenesis of cutaneous T-cell lymphoma (CTCL), and many patients die from complicating bacterial infections. It has been postulated that Chlamydophila pneumoniae ( C. pneumoniae ) infection may be involved in the pathogenesis of Mycosis fungoides (MF) but published data are limited and controversial. Aim: To analyze the frequency of ( C. pneumoniae ) DNA presence in blood samples of lymphoma cases...
June 2018: Postȩpy Dermatologii i Alergologii
https://www.readbyqxmd.com/read/29993279/activated-natural-killer-t-cells-in-mice-induce-acute-kidney-injury-with-hematuria-through-possibly-common-mechanisms-shared-by-human-cd56-t-cells
#9
Takahiro Uchida, Hiroyuki Nakashima, Seigo Ito, Takuya Ishikiriyama, Masahiro Nakashima, Shuhji Seki, Hiroo Kumagai, Naoki Oshima
Although activation of mouse natural killer T (NKT) cells by alpha-galactosylceramide (α-GalCer) causes failure of multiple organs, including the kidneys, precise mechanisms underlying kidney injury remain unclear. Here, we showed that α-GalCer-activated mouse NKT cells injured both kidney vascular endothelial cells and tubular epithelial cells in vitro, causing acute kidney injury (AKI) with hematuria in middle-aged mice. Perforin-mediated pathway was mainly involved in glomerular endothelial cell injury, whereas TNF-α/Fas ligand pathway played an important role in the injury of tubular epithelial cells...
July 11, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29982731/dysfunction-of-circulating-natural-killer-t-cells-in-patients-with-scrub-typhus
#10
Seung-Ji Kang, Hye-Mi Jin, Young-Nan Cho, Tae-Hoon Oh, Seong Eun Kim, Uh Jin Kim, Kyung-Hwa Park, Hee-Chang Jang, Sook-In Jung, Seung-Jung Kee, Yong-Wook Park
Background: Human natural killer T (NKT) cells are known to serve as regulatory and/or effector cells in infectious diseases. However, little is known about the role of NKT cells in Orientia tsutsugamushi infection. Accordingly, the objective of this study was to examine the level and function of NKT cells in patients with scrub typhus. Methods: This study included 62 scrub typhus patients and 62 healthy controls (HCs). NKT cell level and function in peripheral blood samples were measured by flow cytometry...
June 30, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29980684/altered-thymic-differentiation-and-modulation-of-arthritis-by-invariant-nkt-cells-expressing-mutant-zap70
#11
Meng Zhao, Mattias N D Svensson, Koen Venken, Ashu Chawla, Shu Liang, Isaac Engel, Piotr Mydel, Jeremy Day, Dirk Elewaut, Nunzio Bottini, Mitchell Kronenberg
Various subsets of invariant natural killer T (iNKT) cells with different cytokine productions develop in the mouse thymus, but the factors driving their differentiation remain unclear. Here we show that hypomorphic alleles of Zap70 or chemical inhibition of Zap70 catalysis leads to an increase of IFN-γ-producing iNKT cells (NKT1 cells), suggesting that NKT1 cells may require a lower TCR signal threshold. Zap70 mutant mice develop IL-17-dependent arthritis. In a mouse experimental arthritis model, NKT17 cells are increased as the disease progresses, while NKT1 numbers negatively correlates with disease severity, with this protective effect of NKT1 linked to their IFN-γ expression...
July 6, 2018: Nature Communications
https://www.readbyqxmd.com/read/29973929/new-insights-into-the-regulation-of-natural-killer-group-2-member-d-nkg2d-and-nkg2d-ligands-endoplasmic-reticulum-stress-and-cea-related-cell-adhesion-molecule-1
#12
REVIEW
Shuhei Hosomi, Joep Grootjans, Yu-Hwa Huang, Arthur Kaser, Richard S Blumberg
Natural-killer group 2 member D (NKG2D) is a well-characterized activating receptor expressed by natural killer (NK) cells, NKT cells, activated CD8+ T cells, subsets of γδ+ T cells, and innate-like T cells. NKG2D recognizes multiple ligands (NKG2D-ligands) to mount an innate immune response against stressed, transformed, or infected cells. NKG2D-ligand surface expression is tightly restricted on healthy cells through transcriptional and post-transcriptional mechanisms, while transformed or infected cells express the ligands as a danger signal...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29956149/characterization-of-thymic-development-of-natural-killer-t-cell-subsets-by-multiparameter-flow-cytometry
#13
Kathryn D Tuttle, Laurent Gapin
Natural killer T (NKT) cells are a subset of αβ T cells that recognize lipid antigens presented by the nonclassical MHC molecule CD1d. Although numerically small, these cells have been shown to play an important role in the regulation of multiple immune responses, including microbial infection, autoimmunity, and cancer. Even in the steady state, cytokine production by NKT cells influences the basal status and function of other immune cells, including dendritic cells and CD8 T cells. To fully understand their biology and harness them in the clinic, it is imperative to dissect the molecular mechanisms involved in the acquisition of their functionality...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29951695/deviations-in-peripheral-blood-cell-populations-are-associated-with-the-stage-of-primary-biliary-cholangitis-and-presence-of-itching
#14
Halina Cichoż-Lach, Ewelina Grywalska, Agata Michalak, Agnieszka Kowalik, Michał Mielnik, Jacek Roliński
To evaluate the role of Th17, Treg cells, activated T CD3+ and B CD19+ lymphocytes in primary biliary cholangitis (PBC) patients. 40 female patients with PBC and 20 healthy donors were enrolled in this study. The percentages and absolute counts of Th17, Treg, activated T CD3+ , B CD19+ , NK, NKT-like lymphocytes were measured by flow cytometry. Our research revealed significantly lower frequencies and absolute counts of CD4+ CD25+ FOXP3+ Treg cells (p < 0.0001), higher percentages and absolute counts of Th17 cells (IL-17A+ CD3+ CD4+ ; p < 0...
June 27, 2018: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/29951356/glycosphingolipids-prevent-apap-and-hmg-coa-reductase-inhibitors-mediated-liver-damage-a-novel-method-for-safer-drug-formulation-that-prevents-drug-induced-liver-injury
#15
Meir Mizrahi, Tomer Adar, Gadi Lalazar, Dean Nachman, Madi El Haj, Ami Ben Ya'acov, Yoav Lichtenstein, Yehudit Shabat, Dimitri Kanovich, Lida Zolotarov, Yaron Ilan
Background and Aims: Acetaminophen (APAP) and HMG-CoA reductase inhibitors are common causes of drug-induced liver injury (DILI). This study aimed to determine the ability to reduce APAP- and statins-mediated liver injury by using formulations that combine glycosphingolipids and vitamin E. Methods: Mice were injected with APAP or with statins and treated before and after with β-glucosylceramide (GC), with or without vitamin E. Mice were followed for changes in liver enzymes, liver histology, hepatic expression of JNK, STAT3 and caspase 3, as well as intrahepatic natural killer T cells (NKT) and the serum cytokine levels by flow cytometry...
June 28, 2018: Journal of Clinical and Translational Hepatology
https://www.readbyqxmd.com/read/29951065/monocyte-derived-dendritic-cells-differentiated-in-the-presence-of-lenalidomide-display-a-semi-mature-phenotype-enhanced-phagocytic-capacity-and-th1-polarization-capability
#16
Juan López-Relaño, Beatriz Martín-Adrados, Irene Real-Arévalo, Javier Lozano-Bartolomé, Beatriz Abós, Silvia Sánchez-Ramón, Bárbara Alonso, Manuel Gómez Del Moral, Eduardo Martínez-Naves
Lenalidomide is an analog of thalidomide, with potent anticancer activity demonstrated in several hematological malignancies. It has immunomodulatory properties, being able to enhance the activation of different types of immune cells, which results in antitumor activities. Dendritic cells (DCs) are pivotal in the immune response, and different immunotherapeutic approaches targeting these cells are being developed. Since little is known about the effect of lenalidomide on DCs, the goal of the present work was to investigate the phenotype and function of human monocyte-derived DCs differentiated in the presence of lenalidomide (L-DCs)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29948616/il-2-and-il-15-induced-nkg2d-cd158a-and-cd158b-expression-on-t-nkt-like-and-nk-cell-lymphocyte-subsets-from-regional-lymph-nodes-of-melanoma-patients
#17
Ana Vuletić, Irena Jovanić, Vladimir Jurišić, Zorka Milovanović, Srđan Nikolić, Igor Spurnić, Gordana Konjević
Regional lymph nodes (LN)s represent important immunological barriers in spreading of malignant tumors. However, they are the most frequent early metastatic site in melanoma. Immunomodulatory agents including cytokines have been included in therapy of melanoma and have shown severe side effects and toxicity. In this sense, there is a growing need for bringing these agents to further in vitro testing that may enlighten aspects of their regional application. Therefore, the aim of this study was to investigate the effect of interleukin (IL)-2 and IL-15, the two cytokines with similar immune-enhancing effects, on the expression of activating NKG2D, inhibitory CD158a and CD158b receptors on CD8+ T, NKT-like and NK cell lymphocyte subsets from regional LNs of melanoma patients...
June 11, 2018: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/29942311/role-of-natural-killer-t-cells-in-the-development-of-obesity-and-insulin-resistance-insights-from-recent-progress
#18
REVIEW
Masashi Satoh, Kazuya Iwabuchi
Natural killer T (NKT) cells play important roles in adipose tissue inflammation, and thus influence the development of diet-induced obesity and insulin resistance. The interactions between cluster of differentiation (CD)1d and NKT T cell receptor are thought to be critical in this process, as demonstrated in two NKT cell-deficient mouse models-systemic CD1d gene knockout (KO) and prototypic Jα18 KO mice. The latter lacks some repertoires besides invariant (i)NKT cells due to manipulation of the Jα18 gene segment; therefore, the role of iNKT vs...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29940370/%C3%AE-galactosylceramide-and-peptide-based-nano-vaccine-synergistically-induced-a-strong-tumor-suppressive-effectin-melanoma
#19
Vanessa Sainz, Liane I F Moura, Carina Peres, Ana I Matos, Ana S Viana, Angela M Wagner, Julia E Vela Ramirez, Teresa Barata, Manuela Gaspar, Steve Brocchini, Mire Zloh, Nicholas A Peppas, Ronit Satchi-Fainaro, Helena F Florindo
α-Galactosylceramide (GalCer) is a glycolipid widely known as an activator of Natural killer T (NKT) cells, constituting a promising adjuvant against cancer, including melanoma. However, limited clinical outcomes have been obtained so far. This study evaluated the synergy between GalCer and major histocompatibility complex (MHC) class I and MHC class II melanoma-associated peptide antigens and the Toll-Like Receptor (TLR) ligands CpG and monophosphoryl lipid A (MPLA), which we intended to maximize following their co-delivery by a nanoparticle (NP)...
June 22, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29939225/cd1d-dependent-natural-killer-t-cells-attenuate-angiotensin-ii-induced-cardiac-remodeling-via-il-10-signaling-in-mice
#20
Hong-Xia Wang, Wen-Jun Li, Cui-Liu Hou, Song Lai, Yun-Long Zhang, Cui Tian, Hui Yang, Jie Du, Hui-Hua Li
Aims: Cd1d is a member of the cluster of differentiation 1 (CD1) family of glycoproteins expressed on the surface of various antigen-presenting cells, which is recognized by natural killer T (NKT) cells. CD1d-dependent NKT cells play an important role in immune-mediated diseases; but the role of these cells in regulating cardiac remodeling remains unknown. Methods and Results: Cardiac remodeling was induced by angiotensin (Ang) II infusion for 2 weeks. Ang II-induced increase in hypertension, cardiac performance, hypertrophy and fibrosis, inflammatory response and activation of the NF-kB and TGF-β1/Smad2/3 pathways was significantly aggravated in CD1d knockout (CD1dko) mice compared with wild type (WT) mice, but these effects were markedly abrogated in WT mice treated with α-galactosylceramide (αGC), a specific activator of NKT cells...
June 23, 2018: Cardiovascular Research
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