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https://www.readbyqxmd.com/read/28335781/tailored-design-of-nkt-stimulatory-glycolipids-for-polarization-of-immune-responses
#1
REVIEW
Jung-Tung Hung, Jing-Rong Huang, Alice L Yu
Natural killer T (NKT) cell is a distinct population of T lymphocytes that can rapidly release massive amount of Th1 and Th2 cytokines upon the engagement of their T cell receptor with glycolipids presented by CD1d. The secreted cytokines can promote cell-mediated immunity to kill tumor cells and intracellular pathogens, or suppress autoreactive immune cells in autoimmune diseases. Thus, NKT cell is an attractive target for developing new therapeutics to manipulate immune system. The best-known glycolipid to activate NKT cells is α-galactosylceramide (α-GalCer), which has been used as a prototype for designing new NKT stimulatory glycolipids...
March 23, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28322093/peripheral-invariant-natural-killer-t-cell-deficiency-in-metabolically-unhealthy-but-normal-weight-versus-metabolically-healthy-but-obese-individuals
#2
Xiao-Li Wang, Xiang-Yun Chang, Xiao-Xiao Tang, Zhi-Gang Chen, Ting Zhou, Kan Sun
Objective To investigate the proportion of circulating invariant natural killer T (iNKT) cells in four body health types. Methods In this cross-sectional study, participants were classified into four body health types according to the body mass index and metabolic status: metabolically healthy and normal weight (MHNW), metabolically unhealthy but normal weight (MUNW), metabolically healthy but obese (MHO), or metabolically unhealthy and obese (MUO). Demographic and clinical characteristics were measured, and the homeostasis model assessment of insulin resistance (HOMA-IR) and visceral adiposity index (VAI) were calculated...
December 2016: Journal of International Medical Research
https://www.readbyqxmd.com/read/28296542/the-autophagy-machinery-restrains-inkt-cell-activation-through-cd1d1-internalization
#3
Christian W Keller, Monica Loi, Svenja Ewert, Isaak Quast, Romina Theiler, Monique Gannagé, Christian Münz, Gennaro De Libero, Stefan Freigang, Jan D Lünemann
Invariant natural killer T (iNKT) cells are innate T cells with powerful immune regulatory functions that recognize glycolipid antigens presented by the CD1D protein. While iNKT-cell-activating glycolipids are currently being explored for their efficacy to improve immunotherapy against infectious diseases and cancer, little is known about the mechanisms that control CD1D antigen presentation and iNKT cell activation in vivo. CD1D molecules survey endocytic pathways to bind lipid antigens in MHC class II containing compartments (MIICs) before recycling to the plasma membrane...
March 15, 2017: Autophagy
https://www.readbyqxmd.com/read/28295259/applying-the-tor-c-que-in-inkt-cells-a-new-twist-in-an-old-tale
#4
Mihalis Verykokakis, Barbara L Kee
The mammalian Target of Rapamycin (mTOR) protein controls the machinery necessary for T-cell activation, differentiation, and memory formation, as a component of mTOR complex 1 (mTORC1) and mTORC2, which function both downstream and upstream of AKT. Invariant natural killer T (iNKT) cells are a unique T-cell subset that exist in a primed state, capable of rapid activation, and produce large quantities of cytokines. iNKT-cell effector differentiation is dependent on the mTORC1 complex; however, the requirements for mTORC2 in iNKT cells have been controversial...
March 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28294313/suppression-of-murine-tumor-growth-through-cd8-ctls-via-activated-dec-205-dendritic-cells-by-sequential-administration-of-%C3%AE-galactosylceramide-in-vivo
#5
Hideki Kogo, Masumi Shimizu, Yasuyuki Negishi, Eiji Uchida, Hidemi Takahashi
Cancer immunity is mediated through the effective priming and activation of tumor-specific class I major histocompatibility complex (MHC-I) molecule-restricted CD8(+) cytotoxic T lymphocytes (CTLs). DEC-205(+) dendritic cells (DCs) can cross-present the epitope(s) of captured tumor antigens associated with class I MHC molecules alongside co-stimulatory molecules to prime and activate tumor-specific CD8(+) CTLs. Immunosuppressive tolerogenic DCs with reduced co-stimulatory molecules may be a cause of impaired CTL induction...
March 12, 2017: Immunology
https://www.readbyqxmd.com/read/28276165/distribution-of-invariant-natural-killer-t-cells-and-dendritic-cells-in-late-pre-term-birth-without-acute-chorioamnionitis
#6
Yasuyuki Negishi, Yoshio Shima, Toshiyuki Takeshita, Hidemi Takahashi
PROBLEM: Acute chorioamnionitis (aCAM) is an important cause of pre-term birth. However, little is known about the pathogenesis of late pre-term birth without aCAM that was the most common category of pre-term birth. Here we analyze the kinetics of immune cells obtained from the decidua of women with late pre-term births with and without aCAM. METHOD OF STUDY: Deciduas were obtained from women who underwent labor with late pre-term birth without aCAM (PB-n/aCAM) or with aCAM (PB-w/aCAM)...
March 9, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28258199/id2-collaborates-with-id3-to-suppress-invariant-nkt-and-innate-like-tumors
#7
Jia Li, Sumedha Roy, Young-Mi Kim, Shibo Li, Baojun Zhang, Cassandra Love, Anupama Reddy, Deepthi Rajagopalan, Sandeep Dave, Anna Mae Diehl, Yuan Zhuang
Inhibitor of DNA binding (Id) proteins, including Id1-4, are transcriptional regulators involved in promoting cell proliferation and survival in various cell types. Although upregulation of Id proteins is associated with a broad spectrum of tumors, recent studies have identified that Id3 plays a tumor-suppressor role in the development of Burkitt's lymphoma in humans and hepatosplenic T cell lymphomas in mice. In this article, we report rapid lymphoma development in Id2/Id3 double-knockout mice that is caused by unchecked expansion of invariant NKT (iNKT) cells or a unique subset of innate-like CD1d-independent T cells...
March 3, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28221388/synthesis-of-c6-modified-%C3%AE-c-galcer-analogues-as-mouse-and-human-inkt-cell-agonists
#8
Joren Guillaume, Toshiyuki Seki, Tine Decruy, Koen Venken, Dirk Elewaut, Moriya Tsuji, Serge Van Calenbergh
α-GalCer analogues that combine known Th1 polarizing C6''-modifications with a C-glycosidic linkage were synthesized. We employed a protecting group strategy that allowed the preparation of both saturated and unsaturated derivatives with variable C6''-substituents. Selected analogues demonstrate promising activity in mice. Interestingly, the introduction of a 6''-O-pyridinylcarbamoyl substituent to α-C-GalCer restores its antigenicity in human iNKT cells.
February 21, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28219981/the-role-of-natural-killer-t-cells-in-a-mouse-model-with-spontaneous-bile-duct-inflammation
#9
Elisabeth Schrumpf, Xiaojun Jiang, Sebastian Zeissig, Marion J Pollheimer, Jarl Andreas Anmarkrud, Corey Tan, Mark A Exley, Tom H Karlsen, Richard S Blumberg, Espen Melum
Natural killer T (NKT) cells are activated by lipid antigens presented by CD1d molecules and represent a major lymphocyte subset of the liver. NODc3c4 mice spontaneously develop biliary inflammation in extra- and intrahepatic bile ducts. We demonstrated by flow cytometry that invariant NKT (iNKT) cells were more abundant in the thymus, spleen, and liver of NODc3c4 mice compared to NOD mice. iNKT cells in NODc3c4 mice displayed an activated phenotype. Further, NOD and NODCd1d(-/-) mice were irradiated and injected with NODc3c4 bone marrow, and injection of NODc3c4 bone marrow resulted in biliary infiltrates independently of CD1d expression in recipient mice...
February 2017: Physiological Reports
https://www.readbyqxmd.com/read/28212574/the-combined-action-of-mast-cell-chymase-tryptase-and-carboxypeptidase-a3-protects-against-melanoma-colonization-of-the-lung
#10
Mirjana Grujic, Aida Paivandy, Ann-Marie Gustafson, Allan R Thomsen, Helena Öhrvik, Gunnar Pejler
Mast cell secretory granules are densely packed with various bioactive mediators including proteases of chymase, tryptase and CPA3 type. Previous studies have indicated that mast cells can affect the outcome of melanoma but the contribution of the mast cell granule proteases to such effects has not been clear. Here we addressed this issue by assessing mice lacking either the chymase Mcpt4, the tryptase Mcpt6 or carboxypeptidase A3 (Cpa3), as well as mice simultaneously lacking all three proteases, in a model of melanoma dissemination from blood to the lung...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28209751/inkt-cell-defects-in-hhv-8-associated-mcd
#11
Thomas S Uldrick
No abstract text is available yet for this article.
February 16, 2017: Blood
https://www.readbyqxmd.com/read/28208073/temporal-regulation-of-wnt-%C3%AE-catenin-signaling-is-important-for-invariant-nkt-cell-development-and-terminal-maturation
#12
Kalyani Pyaram, Jyoti Misra Sen, Cheong-Hee Chang
The Wnt/β-catenin signaling pathway plays important roles during various cellular functions including survival and proliferation of immune cells. The critical role of this pathway in conventional T cell development is established but little is known about its contributions to innate T cell development. In this study, we found that β-catenin level, an indication of the strength of Wnt/β-catenin signaling, is regulated during invariant NKT (iNKT) cell development. β-catenin levels were greatly increased during iNKT cell selection from double positive thymocytes to Stage 0 of iNKT cell development and during subsequent development to Stage 1...
February 13, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28193627/adoptive-transfer-of-invariant-nkt-cells-as-immunotherapy-for-advanced-melanoma-a-phase-1-clinical-trial
#13
Mark A Exley, Philip Friedlander, Nadia Alatrakchi, Lianne Vriend, Simon C Yue, Tetsuro Sasada, Wanyong Zang, Yo Mizukami, Justice Clark, David Nemer, Ken LeClair, Christine Canning, Heather Daley, Glenn Dranoff, Anita Giobbie-Hurder, F Stephen Hodi, Jerome Ritz, Steven P Balk
PURPOSE: Invariant NKT cells (iNKT) are innate-like CD1d-restricted T cells with immunoregulatory activity in diseases including cancer. iNKT from advanced cancer patients can have reversible defects including IFNγ production, and iNKT IFNγ production may stratify for survival. Previous clinical trials using iNKT cell activating ligand α-galactosylceramide have shown responses. Therefore, a phase 1 clinical trial was performed of autologous in vitro expanded iNKT cells in stage IIIB-IV melanoma...
February 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28177888/hdac4-is-expressed-on-multiple-t-cell-lineages-but-dispensable-for-their-development-and-function
#14
Queping Liu, Xilin Zhang, Congcong Yin, Xing Chen, Zhenggang Zhang, Stephen Brown, Hongfu Xie, Li Zhou, Qing-Sheng Mi
Histone deacetylation, reciprocally mediated by histone deacetylases (HDAC) and acetyltransferases, represents one major form of post-translational modification. Previous research indicates that HDACs play an essential regulatory role in the development of various immune cells. However, the specific function of individual HDACs remains largely unexplored. HDAC4, a member of class II HDACs, profoundly investigated in the nervous system, while the expression profile and function of HDAC4 in T cells are barely known...
February 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28154551/prolonged-activation-of-invariant-natural-killer-t-cells-and-th2-skewed-immunity-in-stroke-patients
#15
Connie H Y Wong, Craig N Jenne, Patrick P Tam, Caroline Léger, Andres Venegas, Karla Ryckborst, Michael D Hill, Paul Kubes
BACKGROUND: Infection is highly prevalent and contribute significantly to mortality of stroke patients. In addition to the well described robust systemic lymphocytopenia and skewed T helper 2 (TH2)-immunity after stroke, emerging experimental evidence demonstrate that the development of infection poststroke is attributed by the activation of invariant natural killer T (iNKT) cells. In this prospective study, we examined the levels of a broad spectrum of inflammatory mediators, the activation status of iNKT cell in the blood of patients with various degree of stroke severity, and investigate whether these parameters differ in patients who later develop poststroke infections...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28152086/nnktt120-an-anti-inkt-cell-monoclonal-antibody-produces-rapid-and-sustained-inkt-cell-depletion-in-adults-with-sickle-cell-disease
#16
Joshua J Field, Elaine Majerus, Kenneth I Ataga, Elliot P Vichinsky, Robert Schaub, Robert Mashal, David G Nathan
Invariant NKT (iNKT) cells can be activated to stimulate a broad inflammatory response. In murine models of sickle cell disease (SCD), interruption of iNKT cell activity prevents tissue injury from vaso-occlusion. NKTT120 is an anti-iNKT cell monoclonal antibody that has the potential to rapidly and specifically deplete iNKT cells and, potentially, prevent vaso-occlusion. We conducted an open-label, multi-center, single-ascending-dose study of NKTT120 to determine its pharmacokinetics, pharmacodynamics and safety in steady-state patients with SCD...
2017: PloS One
https://www.readbyqxmd.com/read/28127757/donor-bone-marrow-cells-are-essential-for-inkt-cell-mediated-foxp3-treg-cell-expansion-in-a-murine-model-of-transplantation-tolerance
#17
Satoshi Miyairi, Toshihito Hirai, Rumi Ishii, Masayoshi Okumi, Shinichi Nunoda, Kenji Yamazaki, Yasuyuki Ishii, Kazunari Tanabe
Mixed chimerism induction is the most reliable method for establishing transplantation tolerance. We previously described a novel treatment using a suboptimal dose of anti-CD40 ligand (anti-CD40L) and liposomal formulation of a ligand for invariant natural killer T cells administered to sub-lethally irradiated recipient mice after donor bone marrow cell (BMC) transfer. Recipient mice treated with this regimen showed expansion of a Foxp3-positive regulatory T(Treg) cell phenotype, and formation of mixed chimera...
January 26, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28121454/igg-antibody-response-elicited-by-a-fully-synthetic-two-component-carbohydrate-based-cancer-vaccine-candidate-with-%C3%AE-galactosylceramide-as-built-in-adjuvant
#18
Xu-Guang Yin, Xiang-Zhao Chen, Wen-Mei Sun, Xiao-Shan Geng, Xiao-Kang Zhang, Jian Wang, Pan-Pan Ji, Zhong-Yin Zhou, Dong Jae Baek, Guang-Fu Yang, Zheng Liu, Jun Guo
A fully synthetic self-adjuvanting cancer vaccine candidate was constructed through covalent conjugation of invariant natural killer T (iNKT) cell ligand α-galactosylceramide (αGalCer) with sialyl Tn (STn), a representative tumor-associated carbohydrate antigen (TACA). This two-component vaccine STn-αGalCer is devoid of antigenic peptide, featuring the well-defined structure with high simplicity. STn-αGalCer showed remarkable efficacy in inducing antibody class switching from IgM to STn-specific IgG. Subtypes of IgG antibody were primarily IgG1 and IgG3...
January 25, 2017: Organic Letters
https://www.readbyqxmd.com/read/28119072/invariant-natural-killer-t-cells-and-mucosal-associated-invariant-t-cells-in-multiple-sclerosis
#19
REVIEW
Elena Bianchini, Sara De Biasi, Anna Maria Simone, Diana Ferraro, Patrizia Sola, Andrea Cossarizza, Marcello Pinti
Multiple sclerosis (MS) is a chronic progressive inflammatory demyelinating disorder of the central nervous system, and in several countries is a leading cause of permanent neurological disability in young adults, particularly women. MS is considered an autoimmune disease, caused by an aberrant immune response to environmental triggers in genetically susceptible subjects. However, the contribution of the innate or of the adaptive immune system to the development and progression of the disease has not yet been fully elucidated...
March 2017: Immunology Letters
https://www.readbyqxmd.com/read/28102220/inkt-cells-need-utx-tra-demethylation
#20
S Harsha Krovi, Laurent Gapin
No abstract text is available yet for this article.
January 19, 2017: Nature Immunology
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