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https://www.readbyqxmd.com/read/29452898/transcriptional-and-epigenetic-regulation-of-innate-like-t-lymphocyte-development
#1
REVIEW
Mihalis Verykokakis, Barbara L Kee
Invariant Natural Killer T (iNKT) cells are a heterogeneous innate T cell population that recognizes lipid antigens. Despite the monospecific nature of their T cell receptor, iNKT cells differentiate into stable sublineages during thymic development, before foreign antigen encounter. How iNKT cell subsets acquire and maintain their functional programs is a central question in innate lymphocyte biology. Global transcriptional and epigenetic profiling of iNKT subsets has provided insights into the internal wiring of these subsets that defines their identity...
February 13, 2018: Current Opinion in Immunology
https://www.readbyqxmd.com/read/29449556/cd1d-dependent-immune-suppression-mediated-by-regulatory-b-cells-through-modulations-of-inkt-cells
#2
K Oleinika, E C Rosser, D E Matei, K Nistala, A Bosma, I Drozdov, C Mauri
Regulatory B cells (Breg) express high levels of CD1d that presents lipid antigens to invariant natural killer T (iNKT) cells. The function of CD1d in Breg biology and iNKT cell activity during inflammation remains unclear. Here we show, using chimeric mice, cell depletion and adoptive cell transfer, that CD1d-lipid presentation by Bregs induces iNKT cells to secrete interferon (IFN)-γ to contribute, partially, to the downregulation of T helper (Th)1 and Th17-adaptive immune responses and ameliorate experimental arthritis...
February 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29434853/intracellular-il-4-and-ifn-%C3%AE-expression-in-inkt-cells-from-patients-with-chronic-lymphocytic-leukemia
#3
Agnieszka Bojarska-Junak, Małgorzata Waldowska, Justyna Woś, Sylwia Chocholska, Iwona Hus, Waldemar Tomczak, Michał Dzik, Marek Hus, Jacek Roliński
Malignant B cells in chronic lymphocytic leukemia serve an essential role in the whole immune response, so their interactions with other immune cells are more complex than observed in solid tumors. The latest study results indicate that the immune dysregulation in chronic lymphocytic leukemia (CLL) also affects a small population of invariant natural killer T cells (iNKT). Using peripheral blood iNKT cells obtained from patients with CLL, the objective of the present study was to assess the intracellular expression of typical cytokines involved in the Th1 (IFN-γ) and Th2 (IL-4) response pathways following stimulation with the iNKT-specific ligand α-galactosylceramide...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29431692/development-of-asthma-in-inner-city-children-possible-roles-of-mait-cells-and-variation-in-the-home-environment
#4
Shilpi Chandra, Gerhard Wingender, Jason A Greenbaum, Archana Khurana, Amin M Gholami, Anusha-Preethi Ganesan, Michael Rosenbach, Katy Jaffee, James E Gern, Robert Wood, George O'Connor, Megan Sandel, Meyer Kattan, Leonard Bacharier, Alkis Togias, Anthony A Horner, Mitchell Kronenberg
Humans have populations of innate-like T lymphocytes with an invariant TCR α-chain that recognize nonpeptide Ags, including invariant NKT (iNKT) cells and mucosal-associated invariant T (MAIT) cells. iNKT cell involvement in human asthma is controversial, whereas there has been little analysis of MAIT cells. Using peripheral blood cells from 110 participants from the Urban Environment and Childhood Asthma (URECA) birth cohort study, these cells were analyzed for number and function. We determined whether iNKT cell or MAIT cell frequency at 1 y is correlated with the cytokine polarization of mainstream CD4+ T cells and/or the development of asthma by age 7 y...
February 5, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29419749/deficiency-of-invariant-natural-killer-t-cells-does-not-protect-against-obesity-but-exacerbates-atherosclerosis-in-ldlr-mice
#5
Savitha Subramanian, Leela Goodspeed, Shari Wang, Yilei Ding, Kevin D O'Brien, Godfrey S Getz, Alan Chait, Catherine A Reardon
Obesity is a chronic inflammatory state characterized by altered levels of adipose tissue immune cell populations. Natural killer T (NKT) cells are CD1d restricted lymphocyte subsets that recognize lipid antigens whose level decreases in obese adipose tissue. However, studies in mice with deficiency or increased levels of NKT cells have yielded contradictory results, so the exact role of these cells in obesity and adipose tissue inflammation is not yet established. We previously showed that Ldlr-/- mice with excess invariant NKT (iNKT) cells demonstrate significant weight gain, adiposity, metabolic abnormalities, and atherosclerosis...
February 8, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29416542/id-proteins-suppress-e2a-driven-invariant-natural-killer-t-cell-development-prior-to-tcr-selection
#6
Sumedha Roy, Amanda J Moore, Cassandra Love, Anupama Reddy, Deepthi Rajagopalan, Sandeep S Dave, Leping Li, Cornelis Murre, Yuan Zhuang
A family of transcription factors known as E proteins, and their antagonists, Id proteins, regulate T cell differentiation at critical developmental checkpoints. Id proteins promote the differentiation of conventional αβ T cells and suppress the expansion of innate-like αβ T cells known as invariant natural killer T (iNKT) cells. However, it remains to be determined whether Id proteins differentially regulate these distinct lineage choices in early stages of T cell development. In this manuscript, we report that in Id-deficient mice, uninhibited activity of the E protein family member E2A mediates activation of genes that support iNKT cell development and function...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29406905/autoimmunity-in-multiple-sclerosis-role-of-sphingolipids-invariant-nkt-cells-and-other-immune-elements-in-control-of-inflammation-and-neurodegeneration
#7
REVIEW
Maria Podbielska, Joan O'Keeffe, Edward L Hogan
Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system. It is classified as being an autoimmune response in the genetically susceptible individual to a persistent but unidentified antigen(s). Both the adaptive and the innate immune systems are likely to contribute significantly to MS pathogenesis. This review summarizes current understanding of the characteristics of MS autoimmunity in the initiation and progression of the disease. In particular we find it timely to classify the autoimmune responses by focusing on the immunogenic features of myelin-derived lipids in MS including molecular mimicry; on alterations of bioactive sphingolipids mediators in MS; and on functional roles for regulatory effector cells, including innate lymphocyte populations, like the invariant NKT (iNKT) cells which bridge adaptive and innate immune systems...
February 15, 2018: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/29405328/orchestrating-liver-repair-a-newly-discovered-function-of-hepatic-inkt-cells
#8
Meng Wang, Cynthia Ju
No abstract text is available yet for this article.
February 5, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29363849/impact-of-th1-th2-cytokine-polarity-induced-by-invariant-nkt-cells-on-the-incidence-of-pregnancy-loss-in-mice
#9
Mari Hoya, Takeshi Nagamatsu, Tatsuya Fujii, Danny J Schust, Hiroko Oda, Naoya Akiba, Takayuki Iriyama, Kei Kawana, Yutaka Osuga, Tomoyuki Fujii
OBJECTIVE: This study aimed to investigate the association of Th1/Th2 polarity induced by CD1d-restricted invariant natural killer T (iNKT) cells with pregnancy outcome. METHODS: Two types of iNKT cell stimulants with different cytokine induction properties, alpha-galactosylceramide (AGC; Th1-biased inducer), and a sphingosine-truncated derivative of AGC (OCH; Th2-biased inducer) were administered to pregnant mice on day 9.5 post-coitus (pc), and the incidence of pregnancy loss was evaluated...
January 24, 2018: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/29363187/gpr65-inhibits-experimental-autoimmune-encephalomyelitis-through-cd4-t-cell-independent-mechanisms-that-include-effects-on-inkt-cells
#10
Rushika C Wirasinha, Dipti Vijayan, Nicola J Smith, Grant P Parnell, Alexander Swarbrick, Robert Brink, Cecile King, Graeme Stewart, David R Booth, Marcel Batten
The G protein-coupled receptor 65 (GPR65) gene has been genetically associated with several autoimmune diseases, including multiple sclerosis (MS). GPR65 is predominantly expressed in lymphoid organs and is activated by extracellular protons. In this study, we tested whether GPR65 plays a functional role in demyelinating autoimmune disease. Using a murine model of MS, experimental autoimmune encephalomyelitis (EAE), we found that Gpr65-deficient mice develop exacerbated disease. CD4+ helper T cells are key drivers of EAE pathogenesis, however, Gpr65 deficiency in these cells did not contribute to the observed exacerbated disease...
December 19, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29345057/sodium-chloride-inhibits-ifn-%C3%AE-%C3%A2-but-not-il-4-production-by-invariant-nkt-cells
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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