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https://www.readbyqxmd.com/read/27930306/mir-17%C3%A2-92-family-clusters-control-inkt-cell-ontogenesis-via-modulation-of-tgf-%C3%AE-signaling
#1
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 5, 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
#2
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...
November 21, 2016: Nature Immunology
https://www.readbyqxmd.com/read/27837018/role-of-dendritic-cell-maturation-factors-produced-by-human-invariant-nkt-cells-in-immune-tolerance
#3
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
#4
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
#5
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
#6
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
#7
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...
November 16, 2016: 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
#8
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
https://www.readbyqxmd.com/read/27799287/cd1d-mediated-activation-of-group-3-innate-lymphoid-cells-drives-il-22-production
#9
Julia Saez de Guinoa, Rebeca Jimeno, Nazanin Farhadi, Peter J Jervis, Liam R Cox, Gurdyal S Besra, Patricia Barral
Innate lymphoid cells (ILCs) are a heterogeneous family of immune cells that play a critical role in a variety of immune processes including host defence against infection, wound healing and tissue repair. Whether these cells are involved in lipid-dependent immunity remains unexplored. Here we show that murine ILCs from a variety of tissues express the lipid-presenting molecule CD1d, with group 3 ILCs (ILC3s) showing the highest level of expression. Within the ILC3 family, natural cytotoxicity triggering receptor (NCR)(-)CCR6(+) cells displayed the highest levels of CD1d...
October 31, 2016: EMBO Reports
https://www.readbyqxmd.com/read/27798616/neutrophils-license-inkt-cells-to-regulate-self-reactive-mouse-b-cell-responses
#10
Thomas Hägglöf, Saikiran K Sedimbi, Jennifer L Yates, Roham Parsa, Briana Hauff Salas, Robert A Harris, Elizabeth A Leadbetter, Mikael C I Karlsson
The innate responsiveness of the immune system is important not only for quick responses to pathogens but also for the initiation and shaping of the subsequent adaptive immune response. Activation via the cytokine IL-18, a product of inflammasomes, gives rise to a rapid response that includes the production of self-reactive antibodies. As increased concentrations of this cytokine are found in inflammatory diseases, we investigated the origin of the B cell response and its regulation. We identified an accumulation of B cell-helper neutrophils in the spleen that interacted with innate-type invariant natural killer T cells (iNKT cells) to regulate B cell responses...
December 2016: Nature Immunology
https://www.readbyqxmd.com/read/27798168/discrete-tcr-binding-kinetics-control-invariant-nkt-cell-selection-and-central-priming
#11
Mayra Cruz Tleugabulova, Nichole K Escalante, Shenglou Deng, Stephanie Fieve, June Ereño-Orbea, Paul B Savage, Jean-Philippe Julien, Thierry Mallevaey
Invariant NKT (iNKT) cells develop and differentiate in the thymus, segregating into iNKT1/2/17 subsets akin to Th1/2/17 classical CD4(+) T cells; however, iNKT TCRs recognize Ags in a fundamentally different way. How the biophysical parameters of iNKT TCRs influence signal strength in vivo and how such signals affect the development and differentiation of these cells are unknown. In this study, we manipulated TCRs in vivo to generate clonotypic iNKT cells using TCR retrogenic chimeras. We report that the biophysical properties of CD1d-lipid-TCR interactions differentially impacted the development and effector differentiation of iNKT cells...
November 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27798147/nkt-cell-hyporesponsiveness-leads-to-unrestrained-accumulation-of-marginal-zone-b-cells-in-hypercholesterolemic-apolipoprotein-e-deficient-mice
#12
Serena Ying Soh, Christelle Faveeuw, Chung Hwee Thiam, Lawrence Han Boon Khoo, Kim Pin Yeo, Sheau Yng Lim, Hwee Ying Lim, Jun Xiang Ng, Veronique Angeli
Recently, the role of B cells in atherosclerosis has gained more attention but studies have mainly focused on B1 and follicular B cell subsets. Therefore, the contribution of marginal zone (MZ) B cells in experimental atherosclerosis remains elusive. In the current study, we examined the MZ B cell compartment in atherosclerotic apoE-deficient (apoE(-/-)) mice and found that hypercholesterolemia in these mice was associated with an increased number and percentage of MZ B cells. This aberrant accumulation of MZ B cells was not associated with alterations in their development or increased proliferation but was due to decreased apoptotic cell death...
October 21, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27782963/th1-and-th17-proinflammatory-profile-characterizes-invariant-natural-killer-t-cells-in-virologically-suppressed-hiv-patients-with-low-cd4-cd8-ratio
#13
Sara De Biasi, Elena Bianchini, Milena Nasi, Margherita Digaetano, Lara Gibellini, Gianluca Carnevale, Vanni Borghi, Giovanni Guaraldi, Marcello Pinti, Cristina Mussini, Andrea Cossarizza
INTRODUCTION: Scanty data exist on the phenotype and functionality of invariant natural killer T (iNKT) cells in HIV-infected (HIV+) patients. METHODS: By flow cytometry, we studied iNKT cells from 54 HIV+ patients who started combined antiretroviral therapy and had undetectable viral load for more than 1 year. Twenty-five maintained a CD4/CD8 ratio less than 0.4, whereas 29 reached a ratio more than 1.1; 32 age-matched and sex-matched patients were healthy controls (CTR)...
November 13, 2016: AIDS
https://www.readbyqxmd.com/read/27782396/phenyl-glycolipids-with-different-glycosyl-groups-exhibit-marked-differences-in-murine-and-human-inkt-cell-activation
#14
Tai-Na Wu, Kun-Hsien Lin, Ying-Ta Wu, Jing-Rong Huang, Jung-Tung Hung, Jen-Chine Wu, Chien-Yu Chen, Kuo-Ching Chu, Nan-Horng Lin, Alice L Yu, Chi-Huey Wong
Glycosphingolipids (GSLs) bearing the α-galactosyl head group and the acyl chain terminated with a phenyl derivative were found to be more potent than α-galactosyl ceramide (αGalCer) to stimulate both murine and human invariant natural killer T (iNKT) cells and to induce antibody isotope switch to IgG. In this study, we replaced the galactosyl group with glucose (αGlc) and its fluoro-analogs, and found that phenyl GSLs with αGlc (C34-Glc) and its fluoro-analog 6F-C34-Glc were stronger than those with αGal in stimulating human iNKT cells but weaker in mice...
October 26, 2016: ACS Chemical Biology
https://www.readbyqxmd.com/read/27740636/pre-transplant-donor-cd4-invariant-nkt-cell-expansion-capacity-predicts-the-occurrence-of-acute-graft-versus-host-disease
#15
M-T Rubio, M Bouillié, N Bouazza, T Coman, H Trebeden-Nègre, A Gomez, F Suarez, D Sibon, A Brignier, E Paubelle, S Nguyen-Khoc, M Cavazzana, O Lantz, M Mohty, S Urien, O Hermine
Clinically useful pre-transplant predictive factors of acute graft-versus-host-disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-SCT) are lacking. We prospectively analyzed HSC graft content in CD34(+), NK, conventional T, regulatory T and invariant NKT (iNKT) cells in 117 adult patients before allo-SCT. Results were correlated with occurrence of aGVHD and relapse. In univariate analysis, iNKT cells were the only graft cell populations associated with occurrence of aGVHD. In multivariate analysis, CD4(-) iNKT/T cell frequency could predict grade II-IV aGVHD in bone marrow and peripheral blood stem cell (PBSC) grafts, while CD4(-) iNKT expansion capacity was predictive in PBSC grafts...
October 14, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27739478/in-vivo-dendritic-cell-targeting-cellular-vaccine-induces-cd4-tfh-cell-dependent-antibody-against-influenza-virus
#16
Satoru Yamasaki, Kanako Shimizu, Kohei Kometani, Maki Sakurai, Masami Kawamura, Shin-Ichiro Fujii
An induction of long-term cellular and humoral immunity is for the goal of vaccines, but the combination of antigens and adjuvant remain unclear. Here, we show, using a cellular vaccine carrying foreign protein antigen plus iNKT cell glycolipid antigen, designated as artificial adjuvant vector cells (aAVCs), that mature XCR1(-) DCs in situ elicit not only ordinal antigen-specific CD4(+)T cells, but also CD4(+) Tfh and germinal center, resulted in inducing long-term antibody production. As a mechanism for leading the long-term antibody production by aAVC, memory CD4(+) Tfh cells but not iNKTfh cells played an important role in a Bcl6 dependent manner...
October 14, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27721447/distinct-gene-expression-patterns-correlate-with-developmental-and-functional-traits-of-inkt-subsets
#17
Hristo Georgiev, Inga Ravens, Charaf Benarafa, Reinhold Förster, Günter Bernhardt
Invariant natural killer T (iNKT) cells comprise a subpopulation of innate lymphocytes developing in thymus. A new model proposes subdividing murine iNKT cells into iNKT1, 2 and 17 cells. Here, we use transcriptome analyses of iNKT1, 2 and 17 subsets isolated from BALB/c and C57BL/6 thymi to identify candidate genes that may affect iNKT cell development, migration or function. We show that Fcɛr1γ is involved in generation of iNKT1 cells and that SerpinB1 modulates frequency of iNKT17 cells. Moreover, a considerable proportion of iNKT17 cells express IL-4 and IL-17 simultaneously...
October 10, 2016: Nature Communications
https://www.readbyqxmd.com/read/27720708/invariant-natural-killer-t-cells-play-dual-roles-in-the-development-of-experimental-autoimmune-uveoretinitis
#18
Masashi Satoh, Ken-Ichi Namba, Nobuyoshi Kitaichi, Noriko Endo, Hirokuni Kitamei, Daiju Iwata, Shigeaki Ohno, Susumu Ishida, Kazunori Onoé, Hiroshi Watarai, Masaru Taniguchi, Tatsuro Ishibashi, Joan Stein-Streilein, Koh-Hei Sonoda, Luc Van Kaer, Kazuya Iwabuchi
Experimental autoimmune uveoretinitis (EAU) represents an experimental model for human endogenous uveitis, which is caused by Th1/Th17 cell-mediated inflammation. Natural killer T (NKT) cells recognize lipid antigens and produce large amounts of cytokines upon activation. To examine the role of NKT cells in the development of uveitis, EAU was elicited by immunization with a peptide from the human interphotoreceptor retinoid-binding protein (hIRBP1-20) in complete Freund's adjuvant and histopathology scores were evaluated in C57BL/6 (WT) and NKT cell-deficient mice...
October 5, 2016: Experimental Eye Research
https://www.readbyqxmd.com/read/27714067/synthesis-self-assembly-and-immunological-activity-of-%C3%AE-galactose-functionalized-dendron-lipid-amphiphiles
#19
John F Trant, Namrata Jain, Delfina M Mazzuca, James T McIntosh, Bo Fan, S M Mansour Haeryfar, Sebastien Lecommandoux, Elizabeth R Gillies
Nanoassemblies presenting multivalent displays of biologically active carbohydrates are of significant interest for a wide array of biomedical applications ranging from drug delivery to immunotherapy. In this study, glycodendron-lipid hybrids were developed as a new and tunable class of dendritic amphiphiles. A modular synthesis was used to prepare dendron-lipid hybrids comprising distearylglycerol and 0 through 4th generation polyester dendrons with peripheral protected amines. Following deprotection of the amines, an isothiocyanate derivative of C-linked α-galactose (α-Gal) was conjugated to the dendron peripheries, affording amphiphiles with 1 to 16 α-Gal moieties...
October 14, 2016: Nanoscale
https://www.readbyqxmd.com/read/27706127/regulatory-t-cells-decrease-invariant-natural-killer-t-cell-mediated-pregnancy-loss-in-mice
#20
L Li, J Tu, Y Jiang, J Zhou, D J Schust
Pregnancy loss is the commonest complication of pregnancy. The causes of pregnancy loss are poorly understood. It has been reported that stimulation of invariant natural killer T (iNKT) cells using α-galactosylceramide (αGC) induces pregnancy loss in mice. Here we investigated the mechanisms, especially the role of regulatory T (Treg) cells, in iNKT cell-mediated pregnancy loss. We found that injection of αGC rapidly induced fetal resorption, activated decidual iNKT cells, decreased the percentage of decidual Treg cells and their interleukin (IL)-10 and transforming growth factor (TGF)-β production, and upregulated the levels of interferon (IFN)-γ, tumor necrosis factor-α, IL-4, and IL-10 in serum...
October 5, 2016: Mucosal Immunology
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