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https://www.readbyqxmd.com/read/29688330/novel-thioglycoside-analogs-of-%C3%AE-galactosylceramide-stimulate-cytotoxicity-and-preferential-th1-cytokine-production-by-human-invariant-natural-killer-t-cells
#1
Ashanty M Melo, Lei Zhang, Éilis F Dockry, Andreea Petrasca, Yasmeen G Ghnewa, Eamon P Breen, Maria E Morrissey, Ciara O'Reilly, Robyn Bruen, Andrew O'Meara, Joanne Lysaght, Xiangming Zhu, Derek G Doherty
Invariant natural killer T (iNKT) cells recognize glycolipid antigens bound to CD1d molecules on antigen-presenting cells. Therapeutic activation of iNKT cells with the xenogeneic glycolipid α-galactosylceramide (α-GalCer) can prevent and reverse tumor growth in murine models, but clinical trials using α-GalCer-stimulated human iNKT cells have shown limited efficacy. We synthesized a series of thioglycoside analogs of α-GalCer with different substituents to the galactose residue and found that two of these compounds, XZ7 and XZ11, bound to CD1d-transfected HeLa cells and activated lines of expanded human iNKT cells...
April 6, 2018: Glycobiology
https://www.readbyqxmd.com/read/29684201/dysregulation-of-epstein-barr-virus-infection-in-hypomorphic-zap70-mutation
#2
Akihiro Hoshino, Takehiro Takashima, Kenichi Yoshida, Akira Morimoto, Yuta Kawahara, Tzu-Wen Yeh, Tsubasa Okano, Motoi Yamashita, Noriko Mitsuiki, Kohsuke Imai, Takashi Sakatani, Atsuko Nakazawa, Yusuke Okuno, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Seishi Ogawa, Seiji Kojima, Tomohiro Morio, Hirokazu Kanegane
Background: Some patients with genetic defects develop Epstein-Barr virus (EBV)-associated lymphoproliferative disorder (LPD)/lymphoma as the main feature. Hypomophic mutations can cause different clinical and laboratory manifestations from null mutations in the same genes. Methods: We sought to describe the clinical and immunologic phenotype of a 21-month-old boy having EBV-associated LPD who was in good health till then. A genetic and immunologic analysis was performed...
April 19, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29680372/inkt-cells-ameliorate-human-autoimmunity-lessons-from-alopecia-areata
#3
Amal Ghraieb, Aviad Keren, Alex Ginzburg, Yehuda Ullmann, Adam G Schrum, Ralf Paus, Amos Gilhar
Alopecia areata (AA) is understood to be a CD8+/NKG2D+ T cell-dependent autoimmune disease. Here, we demonstrate that human AA pathogenesis of is also affected by iNKT10 cells, an unconventional T cell subtype whose number is significantly increased in AA compared to healthy human skin. AA lesions can be rapidly induced in healthy human scalp skin xenotransplants on Beige-SCID mice by intradermal injections of autologous healthy-donor PBMCs pre-activated with IL-2. We show that in this in vivo model, the development of AA lesions is prevented by recognized the iNKT cell activator, α-galactosylceramide (α-GalCer), which stimulates iNKT cells to expand and produce IL-10...
April 18, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29665972/intranasal-delivery-of-influenza-antigen-by-nanoparticles-but-not-nkt-cell-adjuvant-differentially-induces-the-expression-of-b-cell-activation-factors-in-mice-and-swine
#4
Sankar Renu, Santosh Dhakal, Eunsoo Kim, Jonathan Goodman, Yashavanth S Lakshmanappa, Michael J Wannemuehler, Balaji Narasimhan, Prosper N Boyaka, Gourapura J Renukaradhya
Intranasal vaccination of pigs with poly lactic-co-glycolic acid and polyanhydride nanoparticles delivered inactivated influenza virus provides cross-reactive T-cell response, but not antibody response, resulting in incomplete protection and no reduction in nasal virus shedding. Expression of BAFF and Th2 transcription factor GATA-3 were downregulated in lungs of pigs vaccinated with influenza nanovaccine, but in mice it upregulated the expression of BAFF and cytokine TGFβ in cervical lymph nodes. However, the intranasal iNKT cell adjuvant, α-Galctosylceramide upregulates the expression of BAFF in pig lungs...
April 11, 2018: Cellular Immunology
https://www.readbyqxmd.com/read/29664401/histone-deacetylase-7-mediates-tissue-specific-autoimmunity-via-control-of-innate-effector-function-in-invariant-natural-killer-t-cells
#5
Herbert G Kasler, Intelly S Lee, Hyung W Lim, Eric Verdin
We report that Histone Deacetylase 7 (HDAC7) controls the thymic effector programming of Natural Killer T (NKT) cells, and that interference with this function contributes to tissue-specific autoimmunity. Gain of HDAC7 function in thymocytes blocks both negative selection and NKT development, and diverts Vα14/Jα18 TCR transgenic thymocytes into a Tconv-like lineage. Conversely, HDAC7 deletion promotes thymocyte apoptosis and causes expansion of innate-effector cells. Investigating the mechanisms involved, we found that HDAC7 binds PLZF and modulates PLZF-dependent transcription...
April 17, 2018: ELife
https://www.readbyqxmd.com/read/29643189/elevated-hepatic-cd1d-levels-coincide-with-invariant-nkt-cell-defects-in-chronic-hepatitis-b-virus-infection
#6
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/29619756/tissue-specific-phenotype-and-activation-of-inkt-cells-in-morbidly-obese-subjects-interaction-with-adipocytes-and-effect-of-bariatric-surgery
#7
Soledad López, Sara García-Serrano, Carolina Gutierrez-Repiso, Francisca Rodríguez-Pacheco, Ailec Ho-Plagaro, Concepción Santiago-Fernandez, Gonzalo Alba, Marta Cejudo-Guillen, Alberto Rodríguez-Cañete, Sergio Valdes, Lourdes Garrido-Sanchez, David Pozo, Eduardo García-Fuentes
BACKGROUND: The immune response of visceral adipose tissue (VAT) in obesity, in particular the role of invariant natural killer T (iNKT) cells, has not yet been fully elucidated. OBJECTIVE: To characterize iNKT cells and its activation status in VAT and peripheral blood mononuclear cells (PBMC) in morbidly obese subjects (MO), and to analyze their association with metabolic parameters. SUBJECTS AND METHODS: Twenty non-obese and 20 MO subjects underwent Roux-en-Y gastric bypass (RYGB) and were studied before and 6 months after RYGB...
April 4, 2018: Obesity Surgery
https://www.readbyqxmd.com/read/29617191/alpha-galactosylceramide-%C3%AE-galcer-enhances-vaccine-induced-protection-in-a-model-of-ricin-intoxication
#8
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/29610296/distinct-mhc-class-i-like-interacting-invariant-t-cell-lineage-at-the-forefront-of-mycobacterial-immunity-uncovered-in-xenopus
#9
Eva-Stina Edholm, Maureen Banach, Kun Hyoe Rhoo, Martin S Pavelka, Jacques Robert
The amphibian Xenopus laevis is to date the only species outside of mammals where a MHC class I-like (MHC-like) restricted innate-like (i) T cell subset (iVα6 T cells) reminiscent of CD1d-restricted iNKT cells has been identified and functionally characterized. This provides an attractive in vivo model to study the biological analogies and differences between mammalian iT cells and the evolutionarily antecedent Xenopus iT cell defense system. Here, we report the identification of a unique iT cell subset (Vα45-Jα1...
April 2, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29608144/inkt-cells-require-tsc1-for-terminal-maturation-and-effector-lineage-fate-decisions
#10
Jinhong Wu, Jialong Yang, Kai Yang, Hongxia Wang, Balachandra Gorentla, Jinwook Shin, Yurong Qiu, Loretta G Que, W Michael Foster, Zhenwei Xia, Hongbo Chi, Xiao-Ping Zhong
No abstract text is available yet for this article.
April 2, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29602251/tim-3-blockade-promotes-inkt-cell-function-to-inhibit-hbv-replication
#11
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/29593743/therapeutic-potential-of-invariant-natural-killer-t-cells-in-autoimmunity
#12
REVIEW
Luc Van Kaer, Lan Wu
Tolerance against self-antigens is regulated by a variety of cell types with immunoregulatory properties, such as CD1d-restricted invariant natural killer T (iNKT) cells. In many experimental models of autoimmunity, iNKT cells promote self-tolerance and protect against autoimmunity. These findings are supported by studies with patients suffering from autoimmune diseases. Based on these studies, the therapeutic potential of iNKT cells in autoimmunity has been explored. Many of these studies have been performed with the potent iNKT cell agonist KRN7000 or its structural variants...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29582333/influence-of-post-transplant-mucosal-associated-invariant-t-cell-recovery-on-the-development-of-acute-graft-versus-host-disease-in-allogeneic-bone-marrow-transplantation
#13
Koji Kawaguchi, Katsutsugu Umeda, Eitaro Hiejima, Atsushi Iwai, Masamitsu Mikami, Seishiro Nodomi, Satoshi Saida, Itaru Kato, Hidefumi Hiramatsu, Takahiro Yasumi, Ryuta Nishikomori, Tadakazu Kondo, Akifumi Takaori-Kondo, Toshio Heike, Souichi Adachi
Mucosal-associated invariant T (MAIT) and invariant natural killer T (iNKT) cells are T cell subpopulations that possess innate-like properties. We examined the impact of post-hematopoietic stem cell transplantation (HSCT) MAIT and iNKT cell recovery on the clinical outcomes of 69 patients who underwent allogeneic HSCT at Kyoto University Hospital. Multivariate analyses identified the absolute number of MAIT cells (< 0.48/μL on day 60 post-HSCT) as the sole independent risk factor for grade I-IV and grade II-IV acute graft-versus-host disease (aGVHD) among patients who underwent bone marrow transplantation; no correlation was observed between post-HSCT iNKT cell recovery and the development of aGVHD...
March 26, 2018: International Journal of Hematology
https://www.readbyqxmd.com/read/29581354/memory-follicular-helper-invariant-nkt-cells-recognize-lipid-antigens-on-memory-b-cells-and-elicit-antibody-recall-responses
#14
Zuolong Chen, Shasha Zhu, Lu Wang, Di Xie, Huimin Zhang, Xiang Li, Xihua Zheng, Zhiwei Du, Jie Li, Li Bai
Invariant NKT (iNKT) cells have been shown to help B cells in a cognate or noncognate manner; however, whether cognate iNKT cell help induces B cell memory responses remains controversial, and the underlying mechanisms are still unclear. In this study, we demonstrated that, in the absence of follicular helper T cells, cognate iNKT cell help could promote B cell memory responses in mice that were dependent on the formation of memory follicular helper iNKT (iNKTFH ) cells and their interactions with memory B cells in recall responses...
March 26, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
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
#15
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/29559971/novel-approaches-to-exploiting-invariant-nkt-cells-in-cancer-immunotherapy
#16
REVIEW
Benjamin J Wolf, Jiyoung Elizabeth Choi, Mark A Exley
iNKT cells are a subset of innate-like T cells that utilize an invariant TCR alpha chain complexed with a limited repertoire of TCR beta chains to recognize specific lipid antigens presented by CD1d molecules. Because iNKT cells have an invariant TCR, they can be easily identified and targeted in both humans and mice via standard reagents, making this a population of T cells that has been well characterized. iNKT cells are some of the first cells to respond during an infection. By making different types of cytokines in response to different infection stimuli, iNKT cells help determine what kind of immune response then develops...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29539427/bimodal-cd40-fas-dependent-crosstalk-between-inkt-cells-and-tumor-associated-macrophages-impairs-prostate-cancer-progression
#17
Filippo Cortesi, Gloria Delfanti, Andrea Grilli, Arianna Calcinotto, Francesca Gorini, Ferdinando Pucci, Roberta Lucianò, Matteo Grioni, Alessandra Recchia, Fabio Benigni, Alberto Briganti, Andrea Salonia, Michele De Palma, Silvio Bicciato, Claudio Doglioni, Matteo Bellone, Giulia Casorati, Paolo Dellabona
Heterotypic cellular and molecular interactions in the tumor microenvironment (TME) control cancer progression. Here, we show that CD1d-restricted invariant natural killer (iNKT) cells control prostate cancer (PCa) progression by sculpting the TME. In a mouse PCa model, iNKT cells restrained the pro-angiogenic and immunosuppressive capabilities of tumor-infiltrating immune cells by reducing pro-angiogenic TIE2+ , M2-like macrophages (TEMs), and sustaining pro-inflammatory M1-like macrophages. iNKT cells directly contacted macrophages in the PCa stroma, and iNKT cell transfer into tumor-bearing mice abated TEMs, delaying tumor progression...
March 13, 2018: Cell Reports
https://www.readbyqxmd.com/read/29520760/miscarriage-induced-by-adoptive-transfer-of-dendritic-cells-and-invariant-natural-killer-t-cells-into-mice
#18
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/29509047/adipocyte-cd1d-determines-adipose-inflammation-and-insulin-resistance-in-obesity
#19
Jin Young Huh, Yoon Jeong Park, Jae Bum Kim
Obesity-induced adipose tissue inflammation is regulated by various immune cells for innate and adaptive immunity. Among adipose tissue immune cells, it has been proposed that invariant Natural Killer T (iNKT) cells play crucial roles in anti-inflammatory responses in obesity. iNKT cells recognize 'lipid' antigens loaded on CD1d of antigen presenting cells and modulate immune responses by secreting Th1 or Th2 type cytokines depending on species of lipid antigens, antigen presenting cell types, and environmental cytokine milieu...
March 6, 2018: Adipocyte
https://www.readbyqxmd.com/read/29500401/transcription-factor-yy1-is-essential-for-inkt-cell-development
#20
Xijun Ou, Jianxin Huo, Yuhan Huang, Yan-Feng Li, Shengli Xu, Kong-Peng Lam
Invariant natural killer T (iNKT) cells develop from CD4+ CD8+ double-positive (DP) thymocytes and express an invariant Vα 14-Jα 18 T-cell receptor (TCR) α-chain. Generation of these cells requires the prolonged survival of DP thymocytes to allow for Vα 14-Jα 18 gene rearrangements and strong TCR signaling to induce the expression of the iNKT lineage-specific transcription factor PLZF. Here, we report that the transcription factor Yin Yang 1 (YY1) is essential for iNKT cell formation. Thymocytes lacking YY1 displayed a block in iNKT cell development at the earliest progenitor stage...
March 2, 2018: Cellular & Molecular Immunology
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