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https://www.readbyqxmd.com/read/29345057/sodium-chloride-inhibits-ifn-%C3%AE-%C3%A2-but-not-il-4-production-by-invariant-nkt-cells
#1
Dongjin Jeong, Hye Young Kim, Doo Hyun Chung
Invariant NKT (iNKT) cells are a distinct subset of T cells that exert Janus-like functions in vivo by producing IFN-γ and IL-4. Sodium chloride modulates the functions of various immune cells, including conventional CD4+ T cells and macrophages. However, it is not known whether sodium chloride affects iNKT cell function, so we addressed this issue. Sodium chloride inhibited IFN-γ, but not IL-4, production by iNKT cells upon TCR or TCR-independent (IL-12 and IL-18) stimulation in a dose-dependent manner. Consistently, sodium chloride reduced the expression level of tbx21, but not gata-3, in iNKT cells stimulated with TCR engagement or IL-12 + IL-18...
January 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29302250/lineage-differentiation-program-of-invariant-natural-killer-t-cells
#2
REVIEW
Dong-Il Kwon, You Jeong Lee
Invariant natural killer T (iNKT) cells are innate T cells restricted by CD1d molecules. They are positively selected in the thymic cortex and migrate to the medullary area, in which they differentiate into 3 different lineages. Promyelocytic leukemia zinc finger (PLZF) modulates this process, and PLZFhigh, PLZFintermediate, and PLZFlow iNKT cells are designated as NKT2, NKT17, and NKT1 cells, respectively. Analogous to conventional helper CD4 T cells, each subset expresses distinct combinations of transcription factors and produces different cytokines...
December 2017: Immune Network
https://www.readbyqxmd.com/read/29296811/randomized-phase-2-trial-of-regadenoson-for-treatment-of-acute-vaso-occlusive-crises-in-sickle-cell-disease
#3
Joshua J Field, Elaine Majerus, Victor R Gordeuk, Michel Gowhari, Carolyn Hoppe, Matthew M Heeney, Maureen Achebe, Alex George, Hillary Chu, Brian Sheehan, Maneka Puligandla, Donna Neuberg, Gene Lin, Joel Linden, David G Nathan
Adenosine A2A receptor (A2AR) agonists have been shown to decrease tissue inflammation induced by hypoxia/reoxygenation in mice with sickle cell disease (SCD). The key mediator of the A2AR agonist's anti-inflammatory effects is a minor lymphocyte subset, invariant natural killer T (iNKT) cells. We tested the hypothesis that administration of an A2AR agonist in patients with SCD would decrease iNKT cell activation and dampen the severity of vaso-occlusive (VO) crises. In a phase 2, randomized, placebo-controlled trial, we administered a 48-hour infusion of the A2AR agonist regadenoson (1...
September 12, 2017: Blood Advances
https://www.readbyqxmd.com/read/29280974/harnessing-invariant-nkt-cells-to-improve-influenza-vaccines-a-pig-perspective
#4
REVIEW
Guan Yang, Jürgen A Richt, John P Driver
Invariant natural killer T (iNKT) cells are an "innate-like" T cell lineage that recognize glycolipid rather than peptide antigens by their semi-invariant T cell receptors. Because iNKT cells can stimulate an extensive array of immune responses, there is considerable interest in targeting these cells to enhance human vaccines against a wide range of microbial pathogens. However, long overlooked is the potential to harness iNKT cell antigens as vaccine adjuvants for domestic animal species that express the iNKT cell-CD1d system...
December 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29279262/inkt-cells-are-increased-in-children-with-severe-therapy-resistant-asthma
#5
L Antunes, A P Duarte de Souza, P D de Araújo, L A Pinto, M H Jones, R T Stein, P M Pitrez
BACKGROUND: Invariant natural killer T (iNKT) cells play complex functions in the immune system, releasing both Th1 and Th2 cytokines. The role of iNKT cells in human asthma is still controversial and never described in severe therapy-resistant asthma in children. The objective of this work was to analyse iNKT frequency in peripheral blood of children with severe therapy-resistant asthma (STRA), compared to children with milder asthma and healthy controls. METHODS: Children with asthma (n=136) (non-severe and STRA) from a referral centre and healthy controls (n=40) were recruited...
December 23, 2017: Allergologia et Immunopathologia
https://www.readbyqxmd.com/read/29250184/imbalance-in-circulatory-inkt-th17-and-t-regulatory-cell-frequencies-in-patients-with-b-cell-non-hodgkin-s-lymphoma
#6
Iwona Hus, Agnieszka Bojarska-Junak, Marzena Kamińska, Aneta Dobrzyńska-Rutkowska, Karolina Szatan, Agnieszka Szymczyk, Bożena Kukiełka-Budny, Dariusz Szczepanek, Jacek Roliński
T cells are important in B-cell non-Hodgkin's lymphoma immunity, however the function of T cell subsets, including natural killer (iNKT), T helper (Th)17, and T regulatory cells remains to be elucidated. The present study analyzed the frequencies of iNKT, Th17 and T regulatory cells in the peripheral blood of 41 patients with B-cell non-Hodgkin lymphoma at diagnosis, then during and following immunochemotherapy R-CHOP/R-CVP. At lymphoma diagnosis, iNKT and Th17 frequencies were decreased and T regulatory cell frequencies were increased compared with healthy control group...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29247993/interleukin-33-il-33-a-nuclear-cytokine-from-the-il-1-family
#7
REVIEW
Corinne Cayrol, Jean-Philippe Girard
Interleukin-33 (IL-33) is a tissue-derived nuclear cytokine from the IL-1 family abundantly expressed in endothelial cells, epithelial cells and fibroblast-like cells, both during homeostasis and inflammation. It functions as an alarm signal (alarmin) released upon cell injury or tissue damage to alert immune cells expressing the ST2 receptor (IL-1RL1). The major targets of IL-33 in vivo are tissue-resident immune cells such as mast cells, group 2 innate lymphoid cells (ILC2s) and regulatory T cells (Tregs)...
January 2018: Immunological Reviews
https://www.readbyqxmd.com/read/29209308/program-cell-death-receptor-1-mediated-invariant-natural-killer-t-cell-control-of-peritoneal-macrophage-modulates-survival-in-neonatal-sepsis
#8
Eleanor A Fallon, Tristen T Chun, Whitney A Young, Chyna Gray, Alfred Ayala, Daithi S Heffernan
We have shown that invariant natural killer T (iNKT) cells mediate sepsis-induced end-organ changes and immune responses, including macrophage bacterial phagocytosis, a finding regulated by the check point protein program cell death receptor-1 (PD-1). Furthermore, PD-1 mediates mortality in both adult and neonatal murine sepsis as well as in surgical patients. Given our previous findings, we hypothesize that iNKT cells will also modulate neonatal sepsis survival, and that this effect is regulated in part through PD-1...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29204089/subpopulations-of-natural-killer-t-like-cells-before-and-after-surgical-treatment-of-laryngeal-cancer
#9
Janusz Klatka, Ewelina Grywalska, Anna Hymos, Ewelina Krasowska, Michał Mielnik, Dorota Siwicka-Gieroba, Justyna Markowicz, Piotr Trojanowski, Witold Olszański, Jacek Roliński
Introduction: Tumours connected with head and neck comprise about 5% of all tumours. The most frequent histological type of laryngeal carcinoma is squamous cell carcinoma. Different research projects suggest that the role of T lymphocytes might be significant in tumour development. iNKT cells are a new subpopulation of T cells and show cytotoxic activity against tumours. iNKT cells participate in modulating the function of other cells which have anti-tumour properties and secrete cytokines, which have pro-inflammatory and anti-inflammatory effects...
2017: Central-European Journal of Immunology
https://www.readbyqxmd.com/read/29192280/improved-detection-of-cytokines-produced-by-invariant-nkt-cells
#10
Duygu Sag, Müge Özkan, Mitchell Kronenberg, Gerhard Wingender
Invariant Natural killer T (iNKT) cells rapidly produce copious amounts of multiple cytokines after in vivo activation, allowing for the direct detection of a number of cytokines directly ex vivo. However, for some cytokines this approach is suboptimal. Here, we report technical variations that allow the improved detection of IL-4, IL-10, IL-13 and IL-17A ex vivo. Furthermore, we describe an alternative approach for stimulation of iNKT cells in vitro that allows a significantly improved detection of cytokines produced by iNKT cells...
November 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29191573/excessive-interferon-%C3%AE-signaling-in-autoimmunity-alters-glycosphingolipid-processing-in-b-cells
#11
Andy Hee-Meng Tan, Arleen Sanny, Sze-Wai Ng, Ying-Swan Ho, Nurhidayah Basri, Alison Ping Lee, Kong-Peng Lam
Excessive interferon-α (IFN-α) production by innate immune cells is a hallmark of autoimmune diseases. What other cell type secretes IFN-α and how IFN-α affects immune cell metabolism and homeostasis in autoimmunity are largely unclear. Here, we report that autoimmune B cells, arising from two different B cell-specific genetic lesions in mice, secrete IFN-α. In addition, IFN-α, found in abundance in autoimmunity, elicited profound changes in the B cell lipidome, increasing their expression of glycosphingolipids (GSLs) and leading to their CD1d-mediated depletion of iNKT cells in vitro and in vivo...
November 27, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29187357/iap-antagonists-enhance-cytokine-production-from-mouse-and-human-inkt-cells
#12
Eleanor Clancy-Thompson, Lestat Ali, Patrick T Bruck, Mark A Exley, Richard S Blumberg, Glenn Dranoff, Michael Dougan, Stephanie K Dougan
Inhibitor of apoptosis protein (IAP) antagonists are in clinical trials for a variety of cancers, and mouse models show synergism between IAP antagonists and anti-PD-1 immunotherapy. Although IAP antagonists affect the intrinsic signaling of tumor cells, their most pronounced effects are on immune cells and the generation of antitumor immunity. Here we examined the effects of IAP antagonism on T-cell development using mouse fetal thymic organ culture and observed a selective loss of iNKT cells, an effector cell type of potential importance for cancer immunotherapy...
November 29, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/29179729/deficiency-of-innate-like-t-lymphocytes-in-chronic-obstructive-pulmonary-disease
#13
Mariann Szabó, Veronika Sárosi, Zoltán Balikó, Kornélia Bodó, Nelli Farkas, Tímea Berki, Péter Engelmann
BACKGROUND: Based on the phenotypic and functional characteristics unconventional T-lymphocytes such as invariant natural killer T (iNKT) cells and mucosal-associated invariant T (MAIT) cells link the innate and adaptive immune responses. Up to now data are scarce about their involvement in pulmonary disorders including chronic obstructive pulmonary disease (COPD). This study explores simultaneously the frequencies of iNKT and MAIT cells in the peripheral blood and sputum of stable and exacerbating COPD patients...
November 28, 2017: Respiratory Research
https://www.readbyqxmd.com/read/29163518/mixed-signals-co-stimulation-in-invariant-natural-killer-t-cell-mediated-cancer-immunotherapy
#14
REVIEW
Susannah C Shissler, Michael S Lee, Tonya J Webb
Invariant natural killer T (iNKT) cells are an integral component of the immune system and play an important role in antitumor immunity. Upon activation, iNKT cells can directly kill malignant cells as well as rapidly produce cytokines that stimulate other immune cells, making them a front line defense against tumorigenesis. Unfortunately, iNKT cell number and activity are reduced in multiple cancer types. This anergy is often associated with upregulation of co-inhibitory markers such as programmed death-1...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29163493/alpha-galactosylceramide-cd1d-antibody-fusion-proteins-redirect-invariant-natural-killer-t-cell-immunity-to-solid-tumors-and-promote-prolonged-therapeutic-responses
#15
REVIEW
Lianjun Zhang, Alena Donda
Major progress in cancer immunotherapies have been obtained by the use of tumor targeting strategies, in particular with the development of bi-functional fusion proteins such as ImmTacs or BiTes, which engage effector T cells for targeted elimination of tumor cells. Given the significance of invariant natural killer T (iNKT) cells in bridging innate and adaptive immunity, we have developed a bi-functional protein composed of the extracellular part of CD1d molecule that was genetically fused to an scFv fragment from high affinity antibodies against HER2 or CEA...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29163491/suppression-of-natural-killer-cell-activity-by-regulatory-nkt10-cells-aggravates-alcoholic-hepatosteatosis
#16
Kele Cui, Guoxiu Yan, Xiaodong Zheng, Li Bai, Haiming Wei, Rui Sun, Zhigang Tian
We and others have found that the functions of hepatic natural killer (NK) cells are inhibited but invariant NKT (iNKT) cells become activated after alcohol drinking, leaving a possibility that there exists interplay between NK cells and iNKT cells during alcoholic liver disease. Here, in a chronic plus single-binge ethanol consumption mouse model, we observed that NK cells and interferon-γ (IFN-γ) protected against ethanol-induced liver steatosis, as both wild-type (WT) mice treated with anti-asialo GM1 antibody and IFN-γ-deficient GKO mice developed more severe alcoholic fatty livers...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29163480/differentiation-of-il-17-producing-invariant-natural-killer-t-cells-requires-expression-of-the-transcription-factor-c-maf
#17
Jhang-Sian Yu, Michito Hamada, Shigeo Ohtsuka, Keigyou Yoh, Satoru Takahashi, Shi-Chuen Miaw
c-Maf belongs to the large Maf family of transcription factors and plays a key role in the regulation of cytokine production and differentiation of TH2, TH17, TFH, and Tr1 cells. Invariant natural killer T (iNKT) cells can rapidly produce large quantity of TH-related cytokines such as IFN-γ, IL-4, and IL-17A upon stimulation by glycolipid antigens, such as α-galactosylceramide (α-GalCer). However, the role of c-Maf in iNKT cells and iNKT cells-mediated diseases remains poorly understood. In this study, we demonstrate that α-GalCer-stimulated iNKT cells express c-Maf transcript and protein...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29163475/critical-role-for-very-long-chain-sphingolipids-in-invariant-natural-killer-t-cell-development-and-homeostasis
#18
Ashish Saroha, Yael Pewzner-Jung, Natalia S Ferreira, Piyush Sharma, Youenn Jouan, Samuel L Kelly, Ester Feldmesser, Alfred H Merrill, François Trottein, Christophe Paget, Karl S Lang, Anthony H Futerman
The role of sphingolipids (SLs) in the immune system has come under increasing scrutiny recently due to the emerging contributions that these important membrane components play in regulating a variety of immunological processes. The acyl chain length of SLs appears particularly critical in determining SL function. Here, we show a role for very-long acyl chain SLs (VLC-SLs) in invariant natural killer T (iNKT) cell maturation in the thymus and homeostasis in the liver. Ceramide synthase 2-null mice, which lack VLC-SLs, were susceptible to a hepatotropic strain of lymphocytic choriomeningitis virus, which is due to a reduction in the number of iNKT cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29155098/orai1-mutations-abolishing-store-operated-ca-2-entry-cause-anhidrotic-ectodermal-dysplasia-with-immunodeficiency-eda-id
#19
Jayson Lian, Mario Cuk, Sascha Kahlfuss, Lina Kozhaya, Martin Vaeth, Frédéric Rieux-Laucat, Capucine Picard, Melina J Benson, Antonia Jakovcevic, Karmen Bilic, Iva Martinac, Peter Stathopulos, Imre Kacskovics, Thomas Vraetz, Carsten Speckmann, Stephan Ehl, Thomas Issekutz, Derya Unutmaz, Stefan Feske
BACKGROUND: Store-operated Ca(2+) entry (SOCE) through Ca(2+) release-activated Ca(2+) (CRAC) channels is an essential signaling pathway in many cell types. CRAC channels are formed by ORAI1, ORAI2 and ORAI3 proteins and activated by stromal interaction molecule 1 (STIM1) and STIM2. Mutations in ORAI1 and STIM1 genes that abolish SOCE cause a combined immunodeficiency (CID) syndrome that is accompanied by autoimmunity and non-immunological symptoms. OBJECTIVE: Molecular and immunological analysis of patients with CID, anhidrosis and ectodermal dysplasia of unknown etiology...
November 15, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29135830/tissue-resident-lymphocytes-in-solid-organ-transplantation-innocent-passengers-or-the-key-to-organ-transplant-survival
#20
Amy C Prosser, Axel Kallies, Michaela Lucas
Short-term outcomes of solid organ transplantation have improved dramatically over the past several decades; however, long-term survival has remained static over the same time period, and chronic rejection remains a major cause of graft failure. The importance of donor, or 'passenger', lymphocytes to the induction of tolerance to allografts was recognized in the 1990s; however, their precise contribution to graft acceptance or rejection has not been elucidated. Recently, specialized populations of tissue-resident lymphocytes in nonlymphoid organs have been described...
November 14, 2017: Transplantation
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