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https://www.readbyqxmd.com/read/28632753/mait-cells-launch-a-rapid-robust-and-distinct-hyperinflammatory-response-to-bacterial-superantigens-and-quickly-acquire-an-anergic-phenotype-that-impedes-their-cognate-antimicrobial-function-defining-a-novel-mechanism-of-superantigen-induced-immunopathology
#1
Christopher R Shaler, Joshua Choi, Patrick T Rudak, Arash Memarnejadian, Peter A Szabo, Mauro E Tun-Abraham, Jamie Rossjohn, Alexandra J Corbett, James McCluskey, John K McCormick, Olivier Lantz, Roberto Hernandez-Alejandro, S M Mansour Haeryfar
Superantigens (SAgs) are potent exotoxins secreted by Staphylococcus aureus and Streptococcus pyogenes. They target a large fraction of T cell pools to set in motion a "cytokine storm" with severe and sometimes life-threatening consequences typically encountered in toxic shock syndrome (TSS). Given the rapidity with which TSS develops, designing timely and truly targeted therapies for this syndrome requires identification of key mediators of the cytokine storm's initial wave. Equally important, early host responses to SAgs can be accompanied or followed by a state of immunosuppression, which in turn jeopardizes the host's ability to combat and clear infections...
June 2017: PLoS Biology
https://www.readbyqxmd.com/read/28626526/efficient-divergent-synthesis-of-new-immunostimulant-4%C3%A2-modified-%C3%AE-galactosylceramide-analogues
#2
Jonas Janssens, Tine Decruy, Koen Venken, Toshiyuki Seki, Simon Krols, Johan Van der Eycken, Moriya Tsuji, Dirk Elewaut, Serge Van Calenbergh
A synthesis strategy for the swift generation of 4″-modified α-galactosylceramide (α-GalCer) analogues is described, establishing a chemical platform to comprehensively investigate the structure-activity relationships (SAR) of this understudied glycolipid part. The strategy relies on a late-stage reductive ring-opening of a p-methoxybenzylidene (PMP) acetal to regioselectively liberate the 4″-OH position. The expediency of this methodology is demonstrated by the synthesis of a small yet diverse set of analogues, which were tested for their ability to stimulate invariant natural killer T-cells (iNKT) in vitro and in vivo...
June 8, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28618148/mechanisms-underlying-induction-of-allergic-sensitization-by-pru-p-3
#3
Leticia Tordesillas, Nuria Cubells-Baeza, Cristina Gómez-Casado, Cecilia Berin, Vanesa Esteban, Weronika Barcik, Liam O'Mahony, Carmen Ramirez, Luis F Pacios, María Garrido-Arandia, Araceli Díaz-Perales
BACKGROUND: Recently, the nature of the lipid-ligand of Pru p 3, one of the most common plant food allergens in Southern Europe, has been identified as a derivative of the alkaloid camptothecin bound to phytosphingosine. However, the origin of its immunological activity is still unknown. OBJECTIVE: We sought to evaluate the role of the Pru p 3 lipid- ligand in the immunogenic activity of Pru p 3. METHODS: In vitro cultures of different cell types (monocyte-derived dendritic cells (moDCs), PBMCs and epithelial and iNKT-hybridoma cell lines) have been used to determine the immunological capacity of the ligand, by measuring cell proliferation, maturation markers and cytokine production...
June 15, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28618071/histamine-receptor-2-modifies-inkt-cell-activity-within-the-inflamed-lung
#4
R Ferstl, R Frei, W Barcik, E Schiavi, K Wanke, M Ziegler, N Rodriguez-Perez, D Groeger, P Konieczna, S Zeiter, D Nehrbass, Roger Lauener, C A Akdis, L O'Mahony
BACKGROUND: Histamine is a key immunoregulatory mediator and can dampen proinflammatory responses via activation of histamine receptor 2 (H2 R). The aim of this study was to determine the role of H2 R in modulating lung inflammatory responses. METHODS: H2 R was blocked using famotidine or activated using dimaprit in both the ovalbumin (OVA) and house dust mite extract (HDM) murine models of respiratory inflammation. H2 R-deficient animals and CD1d/ H2 R-deficient animals were utilized to examine the CD1d presentation of lipid antigens (αGal-Cer or OCH) to invariant Natural Killer T (iNKT) cells...
June 15, 2017: Allergy
https://www.readbyqxmd.com/read/28612722/-inkt-cells-potential-therapeutic-targets-to-fight-anthrax
#5
Mathieu Le Gars, Michel Haustant, Maria Klezovich-Benard, Christophe Paget, François Trottein, Pierre L Goossens, Jean-Nicolas Tournier
No abstract text is available yet for this article.
May 2017: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/28610792/quantitative-and-qualitative-inkt-repertoire-associations-with-disease-susceptibility-and-outcome-in-macaque-tuberculosis-infection
#6
Andrew Chancellor, Andrew White, Anna S Tocheva, Joe R Fenn, Mike Dennis, Liku Tezera, Akul Singhania, Tim Elliott, Marc Tebruegge, Paul Elkington, Stephan Gadola, Sally Sharpe, Salah Mansour
Correlates of immune protection that reliably predict vaccine efficacy against Mycobacterium tuberculosis (Mtb) infection are urgently needed. Invariant NKT cells (iNKTs) are CD1d-dependent innate T cells that augment host antimicrobial immunity through production of cytokines, including interferon (IFN)-γ and tumour necrosis factor (TNF)-α. We determined peripheral blood iNKT numbers, their proliferative responses and iNKT subset proportions after in vitro antigen expansion by α-galactosylceramide (αGC) in a large cohort of mycobacteria-naïve non-human primates, and macaques from Bacillus Calmette-Guerin (BCG) vaccine and Mtb challenge studies...
July 2017: Tuberculosis
https://www.readbyqxmd.com/read/28596767/reciprocal-crosstalk-between-dendritic-cells-and-natural-killer-t-cells-mechanisms-and-therapeutic-potential
#7
REVIEW
Christian W Keller, Stefan Freigang, Jan D Lünemann
Natural killer T cells carrying a highly conserved, semi-invariant T cell receptor (TCR) [invariant natural killer T (iNKT) cells] are a subset of unconventional T lymphocytes that recognize glycolipids presented by CD1d molecules. Although CD1d is expressed on a variety of hematopoietic and non-hematopoietic cells, dendritic cells (DCs) are key presenters of glycolipid antigen in vivo. When stimulated through their TCR, iNKT cells rapidly secrete copious amounts of cytokines and induce maturation of DCs, thereby facilitating coordinated stimulation of innate and adaptive immune responses...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28576977/monoclonal-invariant-nkt-inkt-cell-mice-reveal-a-role-for-both-tissue-of-origin-and-the-tcr-in-development-of-inkt-functional-subsets
#8
Eleanor Clancy-Thompson, Gui Zhen Chen, Paul M Tyler, Mariah M Servos, Marta Barisa, Patrick J Brennan, Hidde L Ploegh, Stephanie K Dougan
Invariant NKT (iNKT) cell functional subsets are defined by key transcription factors and output of cytokines, such as IL-4, IFN-γ, IL-17, and IL-10. To examine how TCR specificity determines iNKT function, we used somatic cell nuclear transfer to generate three lines of mice cloned from iNKT nuclei. Each line uses the invariant Vα14Jα18 TCRα paired with unique Vβ7 or Vβ8.2 subunits. We examined tissue homing, expression of PLZF, T-bet, and RORγt, and cytokine profiles and found that, although monoclonal iNKT cells differentiated into all functional subsets, the NKT17 lineage was reduced or expanded depending on the TCR expressed...
June 2, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28573337/immunological-characterization-of-a-rigid-%C3%AE-tn-mimetic-on-murine-inkt-and-human-nk-cells
#9
Silvia Fallarini, Alvaro Brittoli, Michele Fiore, Grazia Lombardi, Olivier Renaudet, Barbara Richichi, Cristina Nativi
The ability of a rigid α-Tn mimetic (compound 1) to activate murine invariant natural killer T (iNKT) and human natural killer (NK) cells, two subsets of lymphocytes involved in cancer immunesurveillance, was investigated. For this purpose, the mimetic 1 was properly conjugated to a stearic acid containing glycerol-based phospholipid (compound 5) to be presented, in the context of the conserved non polymorphic major histocompatibility complex class I-like molecules (CD1d), to iNKT cells. On the contrary, the mimetic 1 was conjugated to a multivalent peptide-based scaffold (compound 6) to induce NK cell activation...
June 1, 2017: Glycoconjugate Journal
https://www.readbyqxmd.com/read/28570692/natural-killer-t-cell-sensitization-during-neonatal-respiratory-syncytial-virus-infection-induces-eosinophilic-lung-disease-in-re-infected-adult-mice
#10
Seung Young Lee, Youran Noh, Jung Hyun Goo, Semi Rho, Min Jung Kim, Chang-Yuil Kang, Manki Song, Jae-Ouk Kim
Respiratory syncytial virus (RSV) is a major viral pathogen that causes severe lower respiratory tract infections in infants and the elderly worldwide. Infants with severe RSV bronchiolitis tend to experience more wheezing and asthma in later childhood. Because invariant natural killer T (iNKT) cells are associated with the asthma pathology, we investigated whether neonatal iNKT cells are involved in the aggravation of pulmonary diseases following RSV infection in mice. Intranasal exposure to the iNKT cell ligand α-galactosylceramide (α-GC) with RSV primary infection in neonatal mice elicited neither cytokine production (except for a slight increase of IL-5) nor pulmonary eosinophilia, despite the presence of both CD1d+ cells and NKT cells...
2017: PloS One
https://www.readbyqxmd.com/read/28566883/thiopurine-use-associated-with-reduced-b-and-natural-killer-cells-in-inflammatory-bowel-disease
#11
James D Lord, Donna M Shows
AIM: To identify which blood and mucosal lymphocyte populations are specifically depleted by thiopurine use in vivo. METHODS: The thiopurines azathioprine and 6-mercaptopurine have been a mainstay of inflammatory bowel disease (IBD) therapy for decades, but their mechanism of action in vivo remains obscure. Although thiopurines are lymphotoxic at high doses, and have been reported to cause T cell apoptosis in vitro, their ability to control IBD at lower doses suggests that they may selectively deplete particular lymphocyte populations...
May 14, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28557814/significance-of-frequencies-compositions-and-or-antileukemic-activity-of-dc-stimulated-invariant-nkt-nk-and-cik-cells-on-the-outcome-of-patients-with-aml-all-and-cll
#12
Corinna L Boeck, Daniel C Amberger, Fatemeh Doraneh-Gard, Wishnu Sutanto, Thomas Guenther, Joerg Schmohl, Friedhelm Schuster, Helmut Salih, Florian Babor, Arndt Borkhardt, Helga Schmetzer
Invariant natural killer T (iNKT)/natural killer (NK)/cytokine-induced killer (CIK) cells are important for immune surveillance. (I) Novel combinations of antibody 6B11 (targeting the Vα24-Jα18-invariant T-cell receptor) with CD4/CD8/CD1d/Vα24 for iNKT subset detection and "T/NK cell-like"-iNKT subsets were defined. Compared with healthy peripheral blood mononuclear cells (MNC) (significantly) lower proportions of iNKT cells (6B11/6B11CD3/6B11CD161), NK cells (CD3CD56/CD3CD161), and CIK cells (CD3CD56/CD3CD161) were found in peripheral blood MNC from acute myeloid (AML)/acute myeloid, lymphoid (ALL)/chronic lymphoid leukemia (CLL) patients in acute disease stages...
July 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28550425/cpg-oligonucleotide-mediated-co-stimulation-of-mouse-invariant-natural-killer-t-cells-negatively-regulates-their-activation-status
#13
Raveendra R Kulkarni, Alexander Ian Villanueva, Leah R Read, Jennifer T Brisbin, Siddhartha Kumar Bhaumik, Jonathan LaMarre, Kaja Murali-Krishna, Shayan Sharif
Invariant natural killer T (iNKT) cells play important roles in antimicrobial defense and immune-regulation. We have previously shown that iNKT cells express certain toll-like receptors (TLR), and that TLR co-stimulation of iNKT cells in the presence of suboptimal concentrations of T cell receptor (TCR) agonists enhances cellular activation. In the present study, we investigated the regulatory effects of CpG oligonucleotides in mouse primary hepatic and splenic iNKT cells and in DN32.D3 iNKT cells. We show that CpG treatment of iNKT cells in the presence of higher concentrations of TCR agonists (α-GalCer or anti-CD3 mAb) results in the up-regulation of TLR9 in iNKT cells with a concurrent reduction in their cellular activation, as assessed by their production of IL-2, IL-4 and IFN-γ compared with controls...
May 27, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28549432/dendritic-cells-combined-with-tumor-cells-and-%C3%AE-galactosylceramide-induce-a-potent-therapeutic-and-nk-cell-dependent-antitumor-immunity-in-b-cell-lymphoma
#14
Laura Escribà-Garcia, Carmen Alvarez-Fernández, Marta Tellez-Gabriel, Jorge Sierra, Javier Briones
BACKGROUND: Invariant natural killer T (iNKT) cells are a small population of lymphocytes with unique specificity for glycolipid antigens presented by non-polymorphic CD1d receptor on dendritic cells (DCs). iNKT cells play a central role in tumor immunology since they are implicated in the coordination of innate and adaptive immune responses. These cells can be activated with the prototypic lipid α-galactosylceramide (α-GalCer), stimulating interferon gamma (IFN-γ) production and cytokine secretion, which contribute to the enhancement of T cell activation...
May 26, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28537058/unusual-suspects-in-the-development-of-obesity-induced-inflammation-and-insulin-resistance-nk-cells-inkt-cells-and-ilcs
#15
REVIEW
Beatriz Dal Santo Francisco Bonamichi, Jongsoon Lee
The notion that obesity-induced inflammation mediates the development of insulin resistance in animal models and humans has been gaining strong support. It has also been shown that immune cells in local tissues, in particular in visceral adipose tissue, play a major role in the regulation of obesity-induced inflammation. Specifically, obesity increases the numbers and activation of proinflammatory immune cells, including M1 macrophages, neutrophils, Th1 CD4 T cells, and CD8 T cells, while simultaneously suppressing anti-inflammatory cells such as M2 macrophages, CD4 regulatory T cells, regulatory B cells, and eosinophils...
May 22, 2017: Diabetes & Metabolism Journal
https://www.readbyqxmd.com/read/28526683/autoreactivity-to-sulfatide-by-human-invariant-nkt-cells
#16
Annelein M Stax, Jessica Tuengel, Enrico Girardi, Naoki Kitano, Lenka L Allan, Victor Liu, Dongjun Zheng, William J Panenka, Joren Guillaume, Chi-Huey Wong, Serge van Calenbergh, Dirk M Zajonc, Peter van den Elzen
Invariant NKT (iNKT) cells are innate-like lymphocytes that recognize lipid Ags presented by CD1d. The prototypical Ag, α-galactosylceramide, strongly activates human and mouse iNKT cells, leading to the assumption that iNKT cell physiology in human and mouse is similar. In this article, we report the surprising finding that human, but not mouse, iNKT cells directly recognize myelin-derived sulfatide presented by CD1d. We propose that sulfatide is recognized only by human iNKT cells because of the unique positioning of the 3-O-sulfated β-galactose headgroup...
May 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28490813/leptin-receptor-antagonism-of-inkt-cell-function-a-novel-strategy-to-combat-multiple-myeloma
#17
M Favreau, E Menu, D Gaublomme, K Vanderkerken, S Faict, K Maes, E De Bruyne, S Govindarajan, M Drennan, S Van Calenbergh, X Leleu, L Zabeau, J Tavernier, K Venken, D Elewaut
A hallmark of bone marrow changes with aging is the increase in adipocyte composition, but how this impacts development of multiple myeloma (MM) is unknown. Here, we report the role of the adipokine leptin as master regulator of anti-myeloma tumor immunity by modulating the invariant natural killer T (iNKT) cell function. A marked increase in serum leptin levels and leptin receptor (LR) expression on iNKT cells in MM patients and the 5T33 murine MM model was observed. MM cells and leptin synergistically counteracted anti-tumor functionality of both murine and human iNKT cells...
May 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28486236/human-invariant-natural-killer-t-cells-respond-to-antigen-presenting-cells-exposed-to-lipids-from-olea-europaea-pollen
#18
Beatriz Abos Gracia, Juan López Relaño, Ana Revilla, Lourdes Castro, Mayte Villalba, Beatriz Martín Adrados, Jose Ramon Regueiro, Edgar Fernández-Malavé, Eduardo Martínez Naves, Manuel Gómez Del Moral
BACKGROUND: Allergic sensitization might be influenced by the lipids present in allergens, which can be recognized by natural killer T (NKT) cells on antigen-presenting cells (APCs). The aim of this study was to analyze the effect of olive pollen lipids in human APCs, including monocytes as well as monocyte-derived macrophages (Mϕ) and dendritic cells (DCs). METHODS: Lipids were extracted from olive (Olea europaea) pollen grains. Invariant (i)NKT cells, monocytes, Mϕ, and DCs were obtained from buffy coats of healthy blood donors, and their cell phenotype was determined by flow cytometry...
2017: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/28483562/the-role-of-inkt-cells-on-the-phenotypes-of-allergic-airways-in-a-mouse-model
#19
Lennart K A Lundblad, Nazey Gülec, Matthew E Poynter, Victoria L DeVault, Oliver Dienz, Jonathan E Boyson, Nirav Daphtary, Minara Aliyeva, Jennifer L Ather, Felix Scheuplein, Robert Schaub
iNKT cells and mast cells have both been implicated in the syndrome of allergic asthma through their activation-induced release of Th2 type cytokines and secretion of histamine and other mediators, respectively, which can promote airways hyperresponsiveness (AHR) to agents such as methacholine. However, a mechanistic link between iNKT cells and mast cell recruitment or activation has never been explored. Our objective was to determine whether iNKT cells are necessary for the recruitment of mast cells and if iNKT cells can influence the acute allergen induced bronchoconstriction (AIB) caused by mast cell mediator release...
May 5, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28477190/il-9-production-by-nonconventional-t-helper-cells
#20
Silvia C P Almeida, Luis Graca
IL-9 is a pro-inflammatory cytokine implicated in certain immune-mediated diseases where chronic or acute inflammation of the mucosa plays an important role. Although initially described as being produced by what was then thought to be Th2 cells, it was later described that specialized lymphocyte populations are involved in IL-9 production. In addition to the classical Th9 effector (subset of CD4+ T cells), IL-9 is also produced by nonconventional lymphocytes, namely invariant natural killer T (iNKT) cells and innate lymphoid cells (ILCs)...
2017: Methods in Molecular Biology
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