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Galactosylceramide

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https://www.readbyqxmd.com/read/29643189/elevated-hepatic-cd1d-levels-coincide-with-invariant-nkt-cell-defects-in-chronic-hepatitis-b-virus-infection
#1
Xiaosheng Tan, Yajie Ding, Peng Zhu, Rui Dou, Zhihui Liang, Daofeng Yang, Zhiyong Huang, Wei Wang, Xiongwen Wu, Xiufang Weng
Activation of invariant NKT (iNKT) cells manifests antiviral immune responses in vivo. However, clinical trials have failed to show consistent hepatitis B virus (HBV) DNA reduction postadministration of iNKT cell-specific agonist α-galactosylceramide (α-GalCer). In this study, we aimed to investigate HBV infection-related iNKT cell defects and explore iNKT cell-based therapeutic potential for chronic hepatitis B (CHB). Liver specimens from 30 HBV-infected hepatocellular carcinoma patients were collected for CD1d/hepatitis B surface Ag (HBsAg) staining and/or intrahepatic iNKT cell assay...
April 11, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29617191/alpha-galactosylceramide-%C3%AE-galcer-enhances-vaccine-induced-protection-in-a-model-of-ricin-intoxication
#2
Jennifer L Yates, Elizabeth Leadbetter, Nicholas J Mantis
Alpha-galactosylceramide (αGalCer) is a glycolipid derived from a marine sponge that is a potent activator of both mouse and human invariant natural killer T (iNKT) cells. For that reason, αGalCer is a promising vaccine adjuvant that has been shown to improve both humoral and cellular immunity when co-administered with various vaccines, including candidate vaccines for biodefense. In the current study, we tested the effectiveness of αGalCer as an adjuvant for the clinically-relevant ricin toxin subunit vaccine, RiVax...
April 4, 2018: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29616022/temporal-regulation-of-natural-killer-t-cell-interferon-gamma-responses-by-%C3%AE-catenin-dependent-and-independent-wnt-signaling
#3
Jessica C Kling, Margaret A Jordan, Lauren A Pitt, Jana Meiners, Thao Thanh-Tran, Le Son Tran, Tam T K Nguyen, Deepak Mittal, Rehan Villani, Raymond J Steptoe, Kiarash Khosrotehrani, Stuart P Berzins, Alan G Baxter, Dale I Godfrey, Antje Blumenthal
Natural killer T (NKT) cells are prominent innate-like lymphocytes in the liver with critical roles in immune responses during infection, cancer, and autoimmunity. Interferon gamma (IFN-γ) and IL-4 are key cytokines rapidly produced by NKT cells upon recognition of glycolipid antigens presented by antigen-presenting cells (APCs). It has previously been reported that the transcriptional coactivator β-catenin regulates NKT cell differentiation and functionally biases NKT cell responses toward IL-4, at the expense of IFN-γ production...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29602251/tim-3-blockade-promotes-inkt-cell-function-to-inhibit-hbv-replication
#4
Yong Xu, Zehua Wang, Xianhong Du, Yuan Liu, Xiaojia Song, Tixiao Wang, Siyu Tan, Xiaohong Liang, Lifen Gao, Chunhong Ma
Increased expression of T cell immunoglobulin and mucin domain-3 (Tim-3) on invariant natural killer T (iNKT) cells is reported in chronic hepatitis B virus (HBV) infection. However, whether Tim-3 regulates iNKT cells in chronic HBV condition remains unclear. In this study, our results showed that the expression of Tim-3 was up-regulated on hepatic iNKT cells from HBV-transgenic (Tg) mice or iNKT cells stimulated with α-galactosylceramide (α-Galcer). Compared with Tim-3- iNKT cells, Tim-3+ iNKT cells expressed more IFN-γ, IL-4 and CD107a, indicating a strong relationship between Tim-3 and iNKT cell activation...
March 30, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29599785/cd1d-restricted-type-ii-nkt-cells-reactive-with-endogenous-hydrophobic-peptides
#5
REVIEW
Yusuke Nishioka, Sakiko Masuda, Utano Tomaru, Akihiro Ishizu
NKT cells belong to a distinct subset of T cells that recognize hydrophobic antigens presented by major histocompatibility complex class I-like molecules, such as CD1d. Because NKT cells stimulated by antigens can activate or suppress other immunocompetent cells through an immediate production of a large amount of cytokines, they are regarded as immunological modulators. CD1d-restricted NKT cells are classified into two subsets, namely, type I and type II. CD1d-restricted type I NKT cells express invariant T cell receptors (TCRs) and react with lipid antigens, including the marine sponge-derived glycolipid α-galactosylceramide...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29576533/dual-modifications-of-%C3%AE-galactosylceramide-synergize-to-promote-activation-of-human-invariant-natural-killer-t-cells-and-stimulate-anti-tumor-immunity
#6
Divya Chennamadhavuni, Noemi Alejandra Saavedra-Avila, Leandro J Carreño, Matthew J Guberman-Pfeffer, Pooja Arora, Tang Yongqing, Hui-Fern Koay, Dale I Godfrey, Santosh Keshipeddy, Stewart K Richardson, Srinivasan Sundararaj, Jae Ho Lo, Xiangshu Wen, José A Gascón, Weiming Yuan, Jamie Rossjohn, Jérôme Le Nours, Steven A Porcelli, Amy R Howell
Glycosylceramides that activate CD1d-restricted invariant natural killer T (iNKT) cells have potential therapeutic applications for augmenting immune responses against cancer and infections. Previous studies using mouse models identified sphinganine variants of α-galactosylceramide as promising iNKT cell activators that stimulate cytokine responses with a strongly proinflammatory bias. However, the activities of sphinganine variants in mice have generally not translated well to studies of human iNKT cell responses...
March 9, 2018: Cell Chemical Biology
https://www.readbyqxmd.com/read/29520760/miscarriage-induced-by-adoptive-transfer-of-dendritic-cells-and-invariant-natural-killer-t-cells-into-mice
#7
Yasuyuki Negishi, Tomoko Ichikawa, Toshiyuki Takeshita, Hidemi Takahashi
Unexpected fetal loss is one of the common complications of pregnancy; however, the pathogenesis of many miscarriages, particularly those not associated with infections, is unknown. We previously found that activated DEC-205+ dendritic cells (DCs) and NK1.1+ invariant natural killer T (iNKT) cells are recruited into the myometrium of mice when miscarriage is induced by the intraperitoneal administration of α-galactosylceramide (α-GalCer). Here we demonstrate that the adoptive transfer of DEC-205+ bone marrow-derived DCs cocultured with α-GalCer (DEC-205+ BMDCs-c/w-α-GalCer) directly induced marked fetal loss by syngeneic pregnant C57BL/6 (B6) mice and allogeneic mice (B6 (♀) × BALB/c (♂)), which was accompanied by the accumulation of activated iNKT cells in the myometrium...
March 9, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29500914/crosstalk-between-mesenchymal-stem-cells-and-t-regulatory-cells-is-crucially-important-for-the-attenuation-of-acute-liver-injury
#8
Marina Gazdic, Bojana Simovic Markovic, Aleksandar Arsenijevic, Nemanja Jovicic, Aleksandar Acovic, C Randall Harrell, Crissy Fellabaum, Valentin Djonov, Nebojsa Arsenijevic, Miodrag L Lukic, Vladislav Volarevic
One of the therapeutic options for the treatment of fulminant hepatitis is re-population of intrahepatic regulatory cells since their pool is significantly reduced during acute liver failure. Although it is known that mesenchymal stem cells (MSCs), which have beneficent effects in the therapy of fulminant hepatitis, may promote expansion of T regulatory cells (Tregs) and B regulatory cells (Bregs), the role of these regulatory cells in MSC-mediated attenuation of acute liver injury is unknown. Herewith, we described the molecular mechanisms involved in the crosstalk between MSCs and liver regulatory cells and analyzed the potential of MSC-based therapy for the expansion of intrahepatic regulatory cells in mouse model of acute liver failure...
March 3, 2018: Liver Transplantation
https://www.readbyqxmd.com/read/29449556/cd1d-dependent-immune-suppression-mediated-by-regulatory-b-cells-through-modulations-of-inkt-cells
#9
K Oleinika, E C Rosser, D E Matei, K Nistala, A Bosma, I Drozdov, C Mauri
Regulatory B cells (Breg) express high levels of CD1d that presents lipid antigens to invariant natural killer T (iNKT) cells. The function of CD1d in Breg biology and iNKT cell activity during inflammation remains unclear. Here we show, using chimeric mice, cell depletion and adoptive cell transfer, that CD1d-lipid presentation by Bregs induces iNKT cells to secrete interferon (IFN)-γ to contribute, partially, to the downregulation of T helper (Th)1 and Th17-adaptive immune responses and ameliorate experimental arthritis...
February 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29448959/impaired-t-cell-mediated-hepatitis-in-peroxisome-proliferator-activated-receptor-alpha-ppar%C3%AE-deficient-mice
#10
Ian N Hines, Michael Kremer, Sherri M Moore, Michael D Wheeler
BACKGROUND: Peroxisome proliferator activated receptor alpha (PPARα), a regulator of enzymes involved in β oxidation, has been reported to influence lymphocyte activation. The purpose of this study was to determine whether PPARα plays a role in T cell-mediated hepatitis induced by Concanavalin A (ConA). METHODS: Wild type (wt) or PPARα-deficient (PPARα -/- ) mice were treated with ConA (15 mg/kg) by intravenous injection 0, 10 or 24 h prior to sacrifice and serum and tissue collection for analysis of tissue injury, cytokine response, T cell activation and characterization...
February 15, 2018: Biological Research
https://www.readbyqxmd.com/read/29434853/intracellular-il-4-and-ifn-%C3%AE-expression-in-inkt-cells-from-patients-with-chronic-lymphocytic-leukemia
#11
Agnieszka Bojarska-Junak, Małgorzata Waldowska, Justyna Woś, Sylwia Chocholska, Iwona Hus, Waldemar Tomczak, Michał Dzik, Marek Hus, Jacek Roliński
Malignant B cells in chronic lymphocytic leukemia serve an essential role in the whole immune response, so their interactions with other immune cells are more complex than observed in solid tumors. The latest study results indicate that the immune dysregulation in chronic lymphocytic leukemia (CLL) also affects a small population of invariant natural killer T cells (iNKT). Using peripheral blood iNKT cells obtained from patients with CLL, the objective of the present study was to assess the intracellular expression of typical cytokines involved in the Th1 (IFN-γ) and Th2 (IL-4) response pathways following stimulation with the iNKT-specific ligand α-galactosylceramide...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29409022/dysregulation-of-kupffer-cells-macrophages-and-natural-killer-t-cells-in-steatohepatitis-in-lxr%C3%AE-knockout-male-mice
#12
Kaori Endo-Umeda, Hiroyuki Nakashima, Naoki Umeda, Shuhji Seki, Makoto Makishima
Liver X receptor (LXR) α expression is mainly localized to metabolic tissues, such as the liver, while LXRβ is ubiquitously expressed. LXRα is activated by oxysterols and plays an important role in the regulation of lipid metabolism in metabolic tissues. In macrophages, LXRs stimulate reverse cholesterol transport and regulate immune responses. Although a high cholesterol diet induces severe steatohepatitis in LXRα-knockout (LXRα-KO) mice, the underlying mechanisms linking lipid metabolism and immune responses remain largely unknown...
February 1, 2018: Endocrinology
https://www.readbyqxmd.com/read/29363849/impact-of-th1-th2-cytokine-polarity-induced-by-invariant-nkt-cells-on-the-incidence-of-pregnancy-loss-in-mice
#13
Mari Hoya, Takeshi Nagamatsu, Tatsuya Fujii, Danny J Schust, Hiroko Oda, Naoya Akiba, Takayuki Iriyama, Kei Kawana, Yutaka Osuga, Tomoyuki Fujii
OBJECTIVE: This study aimed to investigate the association of Th1/Th2 polarity induced by CD1d-restricted invariant natural killer T (iNKT) cells with pregnancy outcome. METHODS: Two types of iNKT cell stimulants with different cytokine induction properties, alpha-galactosylceramide (AGC; Th1-biased inducer), and a sphingosine-truncated derivative of AGC (OCH; Th2-biased inducer) were administered to pregnant mice on day 9.5 post-coitus (pc), and the incidence of pregnancy loss was evaluated...
January 24, 2018: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/29351991/differing-roles-of-cd1d2-and-cd1d1-proteins-in-type-i-natural-killer-t-cell-development-and-function
#14
Srinivasan Sundararaj, Jingjing Zhang, S Harsha Krovi, Romain Bedel, Kathryn D Tuttle, Natacha Veerapen, Gurdyal S Besra, Yogesh Khandokar, T Praveena, Jérôme Le Nours, Jennifer L Matsuda, Jamie Rossjohn, Laurent Gapin
MHC class I-like CD1 molecules have evolved to present lipid-based antigens to T cells. Differences in the antigen-binding clefts of the CD1 family members determine the conformation and size of the lipids that are presented, although the factors that shape CD1 diversity remain unclear. In mice, two homologous genes, CD1D1 and CD1D2, encode the CD1d protein, which is essential to the development and function of natural killer T (NKT) cells. However, it remains unclear whether both CD1d isoforms are equivalent in their antigen presentation capacity and functions...
February 6, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29321320/hiv-1-specific-iga-monoclonal-antibodies-from-an-hiv-1-vaccinee-mediate-galactosylceramide-blocking-and-phagocytosis
#15
Saintedym Wills, Kwan-Ki Hwang, Pinghuang Liu, S Moses Dennison, Matthew Zirui Tay, Xiaoying Shen, Justin Pollara, Judith T Lucas, Robert Parks, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayapan, Jaranit Kaewkungwal, Rasmi Thomas, Jerome H Kim, Nelson L Michael, Merlin L Robb, Mike McRaven, David C Montefiori, Thomas J Hope, Hua-Xin Liao, M Anthony Moody, Guido Ferrari, Barton F Haynes, S Munir Alam, Mattia Bonsignori, Georgia D Tomaras
Vaccine-elicited humoral immune responses comprise an array of antibody forms and specificities, with only a fraction contributing to protective host immunity. Elucidation of antibody effector functions responsible for protective immunity against human immunodeficiency virus type 1 (HIV-1) acquisition is a major goal for the HIV-1 vaccine field. Immunoglobulin A (IgA) is an important part of the host defense against pathogens; however, little is known about the role of vaccine-elicited IgA and its capacity to mediate antiviral functions...
April 1, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29311431/evaluation-of-ph-sensitive-fusogenic-polymer-modified-liposomes-co-loaded-with-antigen-and-%C3%AE-galactosylceramide-as-an-anti-tumor-vaccine
#16
Seiji Okazaki, Tadashi Iwasaki, Eiji Yuba, Shinobu Watarai
pH-Sensitive fusogenic polymer-modified (pH-sensitive) liposomes co-loaded with tumor model antigen, ovalbumin (OVA), and adjuvant, α-galactosylceramide (α-GalCer) were fabricated and administered subcutaneously into mice. The ability of pH-sensitive liposomes containing OVA and α-GalCer to stimulate cellular and humoral immune responses in vivo was compared with OVA-encapsulating pH-sensitive liposomes as well as with OVA alone. After immunization, significant OVA-specific antibodies were detected in the serum...
February 9, 2018: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/29277006/hiv-internalization-into-oral-and-genital-epithelial-cells-by-endocytosis-and-macropinocytosis-leads-to-viral-sequestration-in-the-vesicles
#17
Aizezi Yasen, Rossana Herrera, Kristina Rosbe, Kathy Lien, Sharof M Tugizov
Recently, we showed that HIV-1 is sequestered, i.e., trapped, in the intracellular vesicles of oral and genital epithelial cells. Here, we investigated the mechanisms of HIV-1 sequestration in vesicles of polarized tonsil, foreskin and cervical epithelial cells. HIV-1 internalization into epithelial cells is initiated by multiple entry pathways, including clathrin-, caveolin/lipid raft-associated endocytosis and macropinocytosis. Inhibition of HIV-1 attachment to galactosylceramide and heparan sulfate proteoglycans, and virus endocytosis and macropinocytosis reduced HIV-1 sequestration by 30-40%...
February 2018: Virology
https://www.readbyqxmd.com/read/29210987/prophylactic-sublingual-immunization-with-mycobacterium-tuberculosis-subunit-vaccine-incorporating-the-natural-killer-t-cell-agonist-alpha-galactosylceramide-enhances-protective-immunity-to-limit-pulmonary-and-extra-pulmonary-bacterial-burden-in-mice
#18
Arshad Khan, Shailbala Singh, Gloria Galvan, Chinnaswamy Jagannath, K Jagannadha Sastry
Infection by Mycobacterium tuberculosis (Mtb) remains a major global concern and the available Bacillus Calmette-Guerin (BCG) vaccine is poorly efficacious in adults. Therefore, alternative vaccines and delivery strategies focusing on Mtb antigens and appropriate immune stimulating adjuvants are needed to induce protective immunity targeted to the lungs, the primary sites of infections and pathology. We present here evidence in support of mucosal vaccination by the sublingual route in mice using the subunit Mtb antigens Ag85B and ESAT-6 adjuvanted with the glycolipid alpha-galactosylceramide (α-GalCer), a potent natural killer T (NKT) cell agonist...
December 6, 2017: Vaccines
https://www.readbyqxmd.com/read/29202455/a-simple-clinically-relevant-therapeutic-vaccine-shows-long-term-protection-in-an-aggressive-delayed-treatment-b-lymphoma-model
#19
Pallab Pradhan, Jardin Leleux, Jiaying Liu, Krishnendu Roy
Despite initial remission after successful treatments, B lymphoma patients often encounter relapses and resistance causing high mortality. Thus, there is a need to develop therapies that prevent relapse by providing long-term protection and, ultimately, lead to functional cure. In this study, our goal was to develop a simple, clinically relevant, and easily translatable therapeutic vaccine that provides durable immune protection against aggressive B cell lymphoma and identify critical immune biomarkers that are predictive of long-term survival...
November 16, 2017: JCI Insight
https://www.readbyqxmd.com/read/29199207/effects-of-plant-sphingolipids-on-inflammatory-stress-in-differentiated-caco-2-cells
#20
Shinji Yamashita, Takuya Seino, Kazuhiko Aida, Mikio Kinoshita
To determine the mechanism underlying the anti-inflammatory effects of plant sphingolipids, especially plant glucosylceramide (GlcCer), the effects of plant sphingolipids on inflammatory stress in differentiated Caco-2 cells were compared to those of a sphingolipid of animal origin, galactosylceramide (GalCer). Addition of GlcCer or GalCer suppressed cell injury caused lipopolysaccharide (LPS)- and TNF-α-induced inflammatory stress and induction of apoptosis in differentiated Caco-2 cells. There was no difference in the suppressive effect between GlcCer and GalCer...
2017: Journal of Oleo Science
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