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https://www.readbyqxmd.com/read/28096089/tolerogenic-interactions-between-cd8-dendritic-cells-and-nkt-cells-prevent-rejection-of-bone-marrow-and-organ-grafts
#1
David Hongo, Xiaobin Tang, Xiangyue Zhang, Edgar G Engleman, Samuel Strober
The combination of total lymphoid irradiation and anti-T cell antibodies safely induces immune tolerance to combined hematopoietic cell and organ allografts in humans. Our mouse model required host natural killer T (NKT) cells to induce tolerance. Since NKT cells normally depend on signals from CD8+ dendritic cells (DCs) for their activation, we used the mouse model to test the hypothesis that after lymphoid irradiation host CD8+DCs play a requisite role in tolerance induction through interactions with NKT cells...
January 17, 2017: Blood
https://www.readbyqxmd.com/read/28091533/atp-binding-cassette-transporter-abca7-regulates-nkt-cell-development-and-function-by-controlling-cd1d-expression-and-lipid-raft-content
#2
Heba N Nowyhed, Shilpi Chandra, William Kiosses, Paola Marcovecchio, Farah Andary, Meng Zhao, Michael L Fitzgerald, Mitchell Kronenberg, Catherine C Hedrick
ABCA7 is an ABC transporter expressed on the plasma membrane, and actively exports phospholipid complexes from the cytoplasmic to the exocytoplasmic leaflet of membranes. Invariant NKT (iNKT) cells are a subpopulation of T lymphocytes that recognize glycolipid antigens in the context of CD1d-mediated antigen presentation. In this study, we demonstrate that ABCA7 regulates the development of NKT cells in a cell-extrinsic manner. We found that in Abca7(-/-) mice there is reduced expression of CD1d accompanied by an alteration in lipid raft content on the plasma membrane of thymocytes and antigen presenting cells...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28078715/mtorc2-regulates-multiple-aspects-of-nkt-cell-development-and-function
#3
Tammarah Sklarz, Peng Guan, Mercy Gohil, Renee M Cotton, Moyar Q Ge, Angela Haczku, Rupali Das, Martha S Jordan
Invariant NKT (iNKT) cells bridge innate and adaptive immunity by rapidly secreting cytokines and lysing targets following TCR recognition of lipid antigens. Based on their ability to secrete IFN-γ, IL-4 and IL-17A, iNKT-cells are classified as NKT-1, NKT-2 and NKT-17 subsets, respectively. The molecular pathways regulating iNKT-cell fate are not fully defined. Recent studies implicate Rictor, a required component of mTORC2, in the development of select iNKT-cell subsets, however these reports are conflicting...
January 12, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28062695/the-clonal-invariant-nkt-cell-repertoire-in-people-with-type-1-diabetes-is-characterized-by-a-loss-of-clones-expressing-high-affinity-tcrs
#4
Anna S Tocheva, Salah Mansour, Tristan G H Holt, Samuel Jones, Andrew Chancellor, Joseph P Sanderson, Efrem Eren, Tim J Elliott, Richard I G Holt, Stephan D Gadola
Invariant NKT (iNKT) cells in healthy people express iNKT-TCRs with widely varying affinities for CD1d, suggesting different roles for high- and low-affinity iNKT clones in immune regulation. However, the functional implications of this heterogeneity have not yet been determined. Functionally aberrant iNKT responses have been previously demonstrated in different autoimmune diseases, including human type 1 diabetes, but their relationship to changes in the iNKT clonal repertoire have not been addressed. In this study, we directly compared the clonal iNKT repertoire of people with recent onset type 1 diabetes and age- and gender-matched healthy controls with regard to iNKT-TCR affinity and cytokine production...
January 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28060720/inkt-and-memory-b-cells-alterations-in-hhv-8-multicentric-castleman-disease
#5
Zineb Sbihi, Antoine Dossier, David Boutboul, Lionel Galicier, Christophe Parizot, Amandine Emarre, Bénédicte Hoareau, Nicolas Dupin, Anne-Geneviève Marcelin, Anne Oudin, Claire Fieschi, Félix Agbalika, Brigitte Autran, Eric Oksenhendler, Guislaine Carcelain
Human herpesvirus 8 (HHV-8) is the causative agent of Kaposi's sarcoma (KS) and multicentric Castleman disease (MCD), a life-threatening, virally-induced, B-cell lymphoproliferative disorder. HHV-8 is a B-lymphotropic gamma-herpesvirus closely related to the Epstein-Barr virus (EBV). Invariant natural killer T (iNKT) cells are innate-like T cells that play a role in antiviral immunity, specifically in controlling viral replication in EBV-infected B cells. Decline of iNKT cells is associated with age or HIV-infection, both situations associated with HHV-8-related diseases...
November 9, 2016: Blood
https://www.readbyqxmd.com/read/28035011/invariant-nkt-cells-are-pathogenic-in-the-hla-dr4-transgenic-humanized-mouse-model-of-toxic-shock-syndrome-and-can-be-targeted-to-reduce-morbidity
#6
Peter A Szabo, Patrick T Rudak, Joshua Choi, Stacey X Xu, Robert Schaub, Bhagirath Singh, John K McCormick, S M Mansour Haeryfar
During toxic shock syndrome (TSS), bacterial superantigens trigger a polyclonal T cell response leading to a potentially catastrophic 'cytokine storm'. Whether innate-like invariant natural killer T(iNKT) cells, with remarkable immunomodulatory properties, participate in TSS is unclear. Using genetic and cell depletion approaches, we generated iNKT cell-deficient, superantigen-sensitive HLA-DR4-transgenic (DR4tg) mice, which were compared with their iNKT-sufficient counterparts for responsiveness to staphylococcal enterotoxin B(SEB)...
December 29, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28011187/mucosal-associated-invariant-t-cells-are-depleted-and-functionally-altered-in-patients-with-common-variable-immunodeficiency
#7
Serena Arduini, Jean Dunne, Niall Conlon, Conleth Feighery, Derek G Doherty
Common variable immunodeficiency (CVID) is a primary immunoglobulin deficiency characterized by recurrent infections and complications, including autoimmunity, enteropathy, polyclonal lymphocytic infiltration or lymphoid malignancy. Innate T cells can support B cell maturation and antibody production. We investigated the numbers, phenotypes and functions of circulating B cell, γδ T cell, invariant natural killer T (iNKT) cell and mucosal-associated invariant T (MAIT) cell subsets in 23 CVID patients and 27 healthy controls...
December 21, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28005229/engaging-natural-killer-t-cells-as-universal-helpers-for-vaccination
#8
Mary Speir, Ian F Hermans, Robert Weinkove
Conventional vaccine adjuvants enhance peptide-specific T-cell and B-cell responses by modifying peptide stability or uptake or by binding to pattern-recognition receptors on antigen-presenting cells (APCs). This article discusses the application of a distinct mechanism of adjuvant activity: the activation of type I, or invariant, natural killer T (iNKT) cells to drive cellular and humoral immune responses. Using a semi-invariant T-cell receptor (TCR), iNKT cells recognize glycolipid antigens presented on cluster of differentiation (CD)-1d molecules...
December 22, 2016: Drugs
https://www.readbyqxmd.com/read/28003641/systemic-lupus-erythematosus-inkt-cells-guard-the-heart-against-disease
#9
Joanna Collison
No abstract text is available yet for this article.
December 22, 2016: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/27992400/the-histone-demethylase-utx-regulates-the-lineage-specific-epigenetic-program-of-invariant-natural-killer-t-cells
#10
Semir Beyaz, Ji Hyung Kim, Luca Pinello, Michael E Xifaras, Yu Hu, Jialiang Huang, Marc A Kerenyi, Partha P Das, R Anthony Barnitz, Aurelie Herault, Rizkullah Dogum, W Nicholas Haining, Ömer H Yilmaz, Emmanuelle Passegue, Guo-Cheng Yuan, Stuart H Orkin, Florian Winau
Invariant natural killer T cells (iNKT cells) are innate-like lymphocytes that protect against infection, autoimmune disease and cancer. However, little is known about the epigenetic regulation of iNKT cell development. Here we found that the H3K27me3 histone demethylase UTX was an essential cell-intrinsic factor that controlled an iNKT-cell lineage-specific gene-expression program and epigenetic landscape in a demethylase-activity-dependent manner. UTX-deficient iNKT cells exhibited impaired expression of iNKT cell signature genes due to a decrease in activation-associated H3K4me3 marks and an increase in repressive H3K27me3 marks within the promoters occupied by UTX...
December 19, 2016: Nature Immunology
https://www.readbyqxmd.com/read/27984570/inkt-cells-do-a-fat-lot-of-good
#11
Jayati Mookerjee-Basu, Dietmar J Kappes
No abstract text is available yet for this article.
December 16, 2016: Nature Immunology
https://www.readbyqxmd.com/read/27965675/inkt-cells-in-secondary-progressive-multiple-sclerosis-patients-display-pro-inflammatory-profiles
#12
Sara De Biasi, Anna Maria Simone, Milena Nasi, Elena Bianchini, Diana Ferraro, Francesca Vitetta, Lara Gibellini, Marcello Pinti, Cinzia Del Giovane, Patrizia Sola, Andrea Cossarizza
BACKGROUND: Multiple sclerosis (MS), an autoimmune disease with neurodegeneration and inflammation is characterized by several alterations of different T cell subsets. However, few data exist on the role of iNKT lymphocytes. OBJECTIVE: To identify possible changes in the phenotype of iNKT cells in patients with different clinical forms of MS and find alterations in their polyfunctionality [i.e., ability to produce simultaneously up to four cytokines such as IL-17, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and IL-4]...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27930306/mir-17%C3%A2-92-family-clusters-control-inkt-cell-ontogenesis-via-modulation-of-tgf-%C3%AE-signaling
#13
Maya Fedeli, Michela Riba, Jose Manuel Garcia Manteiga, Lei Tian, Valentina Viganò, Grazisa Rossetti, Massimiliano Pagani, Changchun Xiao, Adrian Liston, Elia Stupka, Davide Cittaro, Sergio Abrignani, Paolo Provero, Paolo Dellabona, Giulia Casorati
Invariant natural killer T cells (iNKT) cells are T lymphocytes displaying innate effector functions, acquired through a distinct thymic developmental program regulated by microRNAs (miRNAs). Deleting miRNAs by Dicer ablation (Dicer KO) in thymocytes selectively impairs iNKT cell survival and functional differentiation. To unravel this miRNA-dependent program, we systemically identified transcripts that were differentially expressed between WT and Dicer KO iNKT cells at different differentiation stages and predicted to be targeted by the iNKT cell-specific miRNAs...
December 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27869820/tet-proteins-regulate-the-lineage-specification-and-tcr-mediated-expansion-of-inkt-cells
#14
Ageliki Tsagaratou, Edahí González-Avalos, Sini Rautio, James P Scott-Browne, Susan Togher, William A Pastor, Ellen V Rothenberg, Lukas Chavez, Harri Lähdesmäki, Anjana Rao
TET proteins oxidize 5-methylcytosine in DNA to 5-hydroxymethylcytosine and other oxidation products. We found that simultaneous deletion of Tet2 and Tet3 in mouse CD4(+)CD8(+) double-positive thymocytes resulted in dysregulated development and proliferation of invariant natural killer T cells (iNKT cells). Tet2-Tet3 double-knockout (DKO) iNKT cells displayed pronounced skewing toward the NKT17 lineage, with increased DNA methylation and impaired expression of genes encoding the key lineage-specifying factors T-bet and ThPOK...
January 2017: Nature Immunology
https://www.readbyqxmd.com/read/27837018/role-of-dendritic-cell-maturation-factors-produced-by-human-invariant-nkt-cells-in-immune-tolerance
#15
Hyeong-Woo Lee, Hyun Bae Jie, Paul L Bollyky, David Sarracino, Tong-Soo Kim, Brian S Wilson
In this study, we used the culture supernatant of iNKT cells to identify human myeloid DC maturation factors produced by human CD4(+) iNKT cells. S100A8 had a strong maturation effect. Notably, the recombinant S100A8 protein displayed properties of DC maturation functioning, and the induction of DC differentiation by both the purified and the recombinant protein were blocked by anti-S100A8 and anti-TLR-4 mAbs. DC differentiation induced by anti-major histocompatibility complex class II/CD1d Ab, S100A8, or both was qualitatively indistinguishable from that induced by the coculture of DCs and iNKT cells or via culture supplementation with supernatants from activated CD4(+) iNKT cells...
November 11, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27835062/class-i-restricted-t-cell-associated-molecule-is-a-marker-for-ifn-%C3%AE-producing-inkt-cells-in-healthy-subjects-and-patients-with-type-1-diabetes
#16
Nonantzin Beristain-Covarrubias, Elsy B Canche-Pool, Carlos Ramirez-Velazquez, Juan Carlos Barragan-Galvez, Rita A Gomez-Diaz, Vianney Ortiz-Navarrete
Class I-restricted T cell-associated molecule (CRTAM) is an activation marker expressed on the cell surface of activated invariant natural killer T (iNKT) cells, CD8(+) T cells, and a small subset of CD4(+) T cells. CRTAM has also been associated with a proinflammatory profile in murine CD4(+) T cells. However, CRTAM has not been thoroughly explored in human cells. This work focused on evaluating CRTAM expression in human iNKT lymphocytes after activation with α-galactosylceramide, its widely used specific glycolipid antigen...
November 11, 2016: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/27833166/soluble-%C3%AE-c-cytokine-receptor-suppresses-il-15-signaling-and-impairs-inkt-cell-development-in-the-thymus
#17
Joo-Young Park, Yuna Jo, Eunhee Ko, Megan A Luckey, Yoo Kyoung Park, Se-Ho Park, Jung-Hyun Park, Changwan Hong
The soluble γc protein (sγc) is a naturally occurring splice isoform of the γc cytokine receptor that is produced by activated T cells and inhibits γc cytokine signaling. Here we show that sγc expression is also highly upregulated in immature CD4(+)CD8(+) thymocytes but then downregulated in mature thymocytes. These results indicate a developmentally controlled mechanism for sγc expression and suggest a potential role for sγc in regulating T cell development in the thymus. Indeed, sγc overexpression resulted in significantly reduced thymocyte numbers and diminished expansion of immature thymocytes, concordant to its role in suppressing signaling by IL-7, a critical γc cytokine in early thymopoiesis...
November 11, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27803187/exogenous-activation-of-invariant-natural-killer-t-cells-by-%C3%AE-galactosylceramide-reduces-pneumococcal-outgrowth-and-dissemination-postinfluenza
#18
Adeline Barthelemy, Stoyan Ivanov, Maya Hassane, Josette Fontaine, Béatrice Heurtault, Benoit Frisch, Christelle Faveeuw, Christophe Paget, François Trottein
: Influenza A virus infection can predispose to potentially devastating secondary bacterial infections. Invariant natural killer T (iNKT) cells are unconventional, lipid-reactive T lymphocytes that exert potent immunostimulatory functions. Using a mouse model of postinfluenza invasive secondary pneumococcal infection, we sought to establish whether α-galactosylceramide (α-GalCer [a potent iNKT cell agonist that is currently in clinical development]) could limit bacterial superinfection...
November 1, 2016: MBio
https://www.readbyqxmd.com/read/27801602/a-potent-adjuvant-effect-of-a-cd1d-binding-nkt-cell-ligand-in-human-immune-system-mice
#19
Xiangming Li, Jing Huang, Izumi Kaneko, Min Zhang, Shiroh Iwanaga, Masao Yuda, Moriya Tsuji
OBJECTIVES: A CD1d-binding invariant natural killer T (iNKT)-cell stimulatory glycolipid, namely 7DW8-5, is shown to enhance the efficacy of radiation-attenuated sporozoites (RAS)-based malaria vaccine in mice. In the current study, we aim to determine whether 7DW8-5 can display a potent adjuvant effect in human immune system (HIS) mice. METHODS: HIS-A2/hCD1d mice, which possess both functional human iNKT cells and CD8+ T cells, were generated by the transduction of NSG mice with adeno-associated virus serotype 9 expressing genes that encode human CD1d molecules and HLA-A*0201, followed by the engraftment of human hematopoietic stem cells...
January 2017: Expert Review of Vaccines
https://www.readbyqxmd.com/read/27799307/nkt-cell-deficient-mice-harbor-an-altered-microbiota-that-fuels-intestinal-inflammation-during-chemically-induced-colitis
#20
Thirumahal Selvanantham, Qiaochu Lin, Cynthia Xinyi Guo, Anuradha Surendra, Stephanie Fieve, Nichole K Escalante, David S Guttman, Catherine J Streutker, Susan J Robertson, Dana J Philpott, Thierry Mallevaey
NKT cells are unconventional T cells that respond to self and microbe-derived lipid and glycolipid Ags presented by the CD1d molecule. Invariant NKT (iNKT) cells influence immune responses in numerous diseases. Although only a few studies have examined their role during intestinal inflammation, it appears that iNKT cells protect from Th1-mediated inflammation but exacerbate Th2-mediated inflammation. Studies using iNKT cell-deficient mice and chemically induced dextran sodium sulfate (DSS) colitis have led to inconsistent results...
October 31, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
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