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https://www.readbyqxmd.com/read/28912381/invariant-natural-killer-t-cells-promote-immunogenic-maturation-of-lung-dendritic-cells-in-mouse-models-of-asthma
#1
Qing He, Linlin Liu, Qiaoyu Yang, Ailing Wang, Shuo Chen, Ruiyun Li, Yi Huang, Guqin Zhang, Xuhong Ding, Hongying Yu, Suping Hu, Hanxiang Nie
Our previous study showed that invariant natural killer T (iNKT) cells might act as an adjuvant to promote Th2 inflammatory responses in an OVA-induced mouse model of allergic asthma, but the mechanism remains unknown. To clarify the underlying mechanism through which iNKT cells promote Th2 inflammatory responses, we investigated the modulatory influence of iNKT cells on phenotypic and functional maturation of lung dendritic cells (LDCs) using iNKT cell-knockout mice, specific iNKT cell activation, co-culture experiments, and adoptive transfer of iNKT cells in mouse models of asthma...
September 14, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28898395/endogenous-lipid-antigens-for-invariant-natural-killer-t-cells-hold-the-reins-in-adipose-tissue-homeostasis
#2
REVIEW
Robert J van Eijkeren, Olga Krabbe, Marianne Boes, Henk S Schipper, Eric Kalkhoven
The global obesity epidemic and its associated co-morbidities, including type 2 diabetes, cardiovascular disease and certain types of cancers, have drawn attention to the pivotal role of adipocytes in health and disease. Besides their 'classical' function in energy storage and release, adipocytes interact with adipose-tissue resident immune cells, among which lipid-responsive invariant Natural Killer T (iNKT) cells. iNKT cells are activated by lipid antigens presented by antigen-presenting cells (APC) as CD1d/lipid complexes...
September 12, 2017: Immunology
https://www.readbyqxmd.com/read/28893990/cd1d-restricted-pathways-in-hepatocytes-control-local-natural-killer-t-cell-homeostasis-and-hepatic-inflammation
#3
Sebastian Zeissig, Kenneth Peuker, Shankar Iyer, Thomas Gensollen, Stephanie K Dougan, Torsten Olszak, Arthur Kaser, Richard S Blumberg
Invariant natural killer T (iNKT) cells recognize lipid antigens presented by CD1d and play a central role in regulating immunity and inflammation in peripheral tissues. However, the mechanisms which govern iNKT cell homeostasis after thymic emigration are incompletely understood. Here we demonstrate that microsomal triglyceride transfer protein (MTP), a protein involved in the transfer of lipids onto CD1d, regulates liver iNKT cell homeostasis in a manner dependent on hepatocyte CD1d. Mice with hepatocyte-specific loss of MTP exhibit defects in the function of CD1d and show increased hepatic iNKT cell numbers as a consequence of altered iNKT cell apoptosis...
September 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28892129/invariant-natural-killer-t-cell-development-and-function-with-loss-of-microrna-155
#4
Adolfo B Frias, Heather M Buechel, Arpan Neupane, Louise M D'Cruz
Invariant Natural Killer T (iNKT) cells are adaptive T cells with innate-like characteristics including rapid cytokine production and proliferative response to stimulation. Development of these cells in the thymus is dependent on expression of the microRNA (miRNA) processing enzyme Dicer indicating iNKT cells likely have distinct miRNA requirements for gene regulation during development. The miRNA, miR-155, has previously been shown to have numerous roles in T cells, including regulation of proliferation and differentiation and positive modulation of IFN-γ expression...
September 11, 2017: Immunology
https://www.readbyqxmd.com/read/28874772/antibody-dependent-fragmentation-is-a-newly-identified-mechanism-of-cell-killing-in-vivo
#5
Pei Xiong Liew, Jung Hwan Kim, Woo-Yong Lee, Paul Kubes
The prevailing view is that therapeutic antibodies deplete cells through opsonization and subsequent phagocytosis, complement-dependent lysis or antibody-dependent cellular-cytotoxicity. We used high resolution in vivo imaging to identify a new antibody-dependent cell death pathway where Kupffer cells ripped large fragments off crawling antibody-coated iNKT cells. This antibody-dependent fragmentation process resulted in lethality and depletion of crawling iNKT cells in the liver sinusoids and lung capillaries...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28860937/a-brief-review-of-clinical-trials-involving-manipulation-of-invariant-nkt-cells-as-a-promising-approach-in-future-cancer-therapies
#6
REVIEW
Małgorzata Waldowska, Agnieszka Bojarska-Junak, Jacek Roliński
In the recent years researchers have put a lot of emphasis on the possible immunotherapeutic strategies able to target tumors. Many studies have proven that the key role in recognition and eradication of cancer cells, both for mice and humans, is being conducted by the invariant natural killer T-cells (NKT). This small subpopulation of lymphocytes can kill other cells, either directly or indirectly, through the natural killer cells' (NK) activation. They can also swiftly release cytokines, causing the involvement of elements of the innate and acquired immune system...
2017: Central-European Journal of Immunology
https://www.readbyqxmd.com/read/28859982/role-of-interleukin-il-17-and-t-helper-th-17%C3%A2-cells-in-cancer
#7
Yang Song, Jian Ming Yang
Interleukin-17 (IL-17), a pleiotropic proinflammatory cytokine, is reported to be significantly generated by a distinct subset of CD4(+) T-cells, upgrading cancer-elicited inflammation and preventing cancer cells from immune surveillance. T-helper (Th)17 cells produced from naive CD4(+) T cells have recently been renowned and generally accepted, gaining eminence in cancer studies and playing the effective role in context of cancer. Th17 cells are the main source of IL-17-secreting cells, It was found that other cell types produced this cytokine as well, including Group 3 innate lymphoid cells (ILC3), δγT cells, invariant natural killer T (iNKT) cells, lymphoid-tissue inducer (LTi)-like cells and Natural killer (NK) cells...
August 30, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28852174/activation-of-invariant-natural-killer-t-cells-stimulated-with-microbial-%C3%AE-mannosyl-glycolipids
#8
Michio Shimamura, Masaki Yamamura, Tatsuya Nabeshima, Naoki Kitano, Peter van den Elzen, Hasan Yesilkaya, Peter Andrew, Petr Illarionov
Some synthetic and bacterial glycolipids presented by CD1d specifically activate invariant NKT (iNKT) cells bearing an invariant Vα14-Jα18 (mouse) or Vα24-Jα18 (human) TCR. The antigenic glycolipids identified to date consist of two hydrophobic chains and an α-glycoside in which the 2'-OH group is in the cis orientation toward the anomeric group, namely, either an α-galactoside or an α-glucoside. Several microbial α-mannosyl glycolipids, in which the 2'-OH group is in the trans orientation, were herein examined to establish whether they have potential to activate iNKT cells...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811651/inkt-cells-prevent-obesity-induced-hepatic-steatosis-in-mice-in-a-c-c-chemokine-receptor-7-dependent-manner
#9
H M Kim, R Lee, E S Lee, M H Kwon, J H Huh, B-E Kwon, E-K Park, S-Y Chang, M-N Kweon, P-H Kim, H-J Ko, C H Chung
Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis are characterized by an increase in hepatic triglyceride content with infiltration of immune cells, which can cause steatohepatitis and hepatic insulin resistance. C-C chemokine receptor 7 (CCR7) is primarily expressed in immune cells, and CCR7 deficiency leads to the development of multi-organ autoimmunity, chronic renal disease, and autoimmune diabetes. Here, we investigated the effect of CCR7 on hepatic steatosis in a mouse model and its underlying mechanism...
August 16, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28783690/cross-talk-between-inkt-cells-and-monocytes-triggers-an-atheroprotective-immune-response-in-sle-patients-with-asymptomatic-plaque
#10
Edward Smith, Sara Croca, Kirsty E Waddington, Reecha Sofat, Maura Griffin, Andrew Nicolaides, David A Isenberg, Ines Pineda Torra, Anisur Rahman, Elizabeth C Jury
Accelerated atherosclerosis is a complication of the autoimmune rheumatic disease systemic lupus erythematosus (SLE). We questioned the role played by invariant natural killer T (iNKT) cells in this process because they not only are defective in autoimmunity but also promote atherosclerosis in response to CD1d-mediated lipid antigen presentation. iNKT cells from SLE patients with asymptomatic plaque (SLE-P) had increased proliferation and interleukin-4 production compared with those from SLE patients with no plaque...
December 2, 2016: Science Immunology
https://www.readbyqxmd.com/read/28780376/retinoic-acid-induction-of-cd1d-expression-primes-chronic-lymphocytic-leukemia-b-cells-for-killing-by-cd8-invariant-natural-killer-t-cells
#11
Yasmeen G Ghnewa, Vincent P O'Reilly, Elisabeth Vandenberghe, Paul V Browne, Anthony M McElligott, Derek G Doherty
Invariant natural killer T (iNKT) cells are cytotoxic T cells that respond to glycolipid antigens presented by CD1d. Therapeutic activation of iNKT cells with α-galactosylceramide (α-GalCer) can prevent and reverse tumor growth in mice and clinical trials involving α-GalCer-stimulated iNKT cells are ongoing in humans. B cells express CD1d, however, we show that CD1d expression is reduced on B cells from patients with chronic lymphocytic leukemia (CLL). B cells from CLL patients pulsed with α-GalCer failed to stimulate cytolytic degranulation by iNKT cell lines, but could present the more potent glycolipid analogue, 7DW8-5...
August 3, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28766890/inkt-cell-activation-plus-t-cell-transfer-establishes-complete-chimerism-in-a-murine-sublethal-bone-marrow-transplant-model
#12
Rumi Ishii, Toshihito Hirai, Satoshi Miyairi, Kazuya Omoto, Masayoshi Okumi, Yasuyuki Ishii, Kazunari Tanabe
Transplant tolerance induction makes it possible to preserve functional grafts for a lifetime without immunosuppressants. One powerful method is to generate mixed hematopoietic chimeras in recipients by adoptive transfer of donor-derived bone marrow cells (BMCs). In our murine transplantation model, we established a novel method for mixed chimera generation using sublethal irradiation, CD40-CD40L blockade, and invariant natural killer T-cell activation. However, numerous BMCs that are required to achieve stable chimerism makes it difficult to apply this model for human transplantation...
August 2, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28765611/the-differentiation-of-ror-%C3%AE-t-expressing-inkt17-cells-is-orchestrated-by-runx1
#13
Puspa Thapa, Bryce Manso, Ji Young Chung, Sinibaldo Romera Arocha, Hai-Hui Xue, Derek B Sant' Angelo, Virginia Smith Shapiro
iNKT cells are a unique lineage of T cells that recognize glycolipid presented by CD1d. In the thymus, they differentiate into iNKT1, iNKT2 and iNKT17 effector subsets, characterized by preferential expression of Tbet, Gata3 and ROR-γt and production of IFN-γ, IL-4 and IL-17, respectively. We demonstrate that the transcriptional regulator Runx1 is essential for the generation of ROR-γt expressing iNKT17 cells. PLZF-cre Runx1 cKO mice lack iNKT17 cells in the thymus, spleen and liver. Runx1-deficient iNKT cells have altered expression of several genes important for iNKT17 differentiation, including decreased expression of IL-7Rα, BATF and c-Maf and increased expression of Bcl11b and Lef1...
August 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28761130/lipodystrophy-and-obesity-are-associated-with-decreased-number-of-t-cells-with-regulatory-function-and-pro-inflammatory-macrophage-phenotype
#14
S Berger, G Ceccarini, G Scabia, I Barone, C Pelosini, F Ferrari, S Magno, A Dattilo, L Chiovato, P Vitti, F Santini, M Maffei
BACKGROUND/OBJECTIVES: In lipodystrophy (LD) adipose tissue function to store lipids is impaired, leading to metabolic syndrome, similar to that found in obesity. Emerging evidence links dysmetabolism with disorders of the immune system. Our aim is to investigate whether T-cell populations with regulatory function and monocyte-derived macrophages (MDMs) are affected by LD and obesity. SUBJECTS/METHODS: Blood was collected from 16 LD, 16 obese (OB, BMI>30 kg m(-2)) and 16 healthy normal-weight women (CNT)...
July 10, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28758901/stromal-cell-cadherin-11-regulates-adipose-tissue-inflammation-and-diabetes
#15
Sook Kyung Chang, Ayano C Kohlgruber, Fumitaka Mizoguchi, Xavier Michelet, Benjamin J Wolf, Kevin Wei, Pui Y Lee, Lydia Lynch, Danielle Duquette, Victòria Ceperuelo-Mallafré, Alexander S Banks, Michael B Brenner
M2 macrophages, innate lymphoid type 2 cells (ILC2s), eosinophils, Tregs, and invariant NK T cells (iNKT cells) all help to control adipose tissue inflammation, while M1 macrophages, TNF, and other inflammatory cytokines drive inflammation and insulin resistance in obesity. Stromal cells regulate leukocyte responses in lymph nodes, but the role of stromal cells in adipose tissue inflammation is unknown. PDGFRα+ stromal cells are major producers of IL-33 in adipose tissue. Here, we show that mesenchymal cadherin-11 modulates stromal fibroblast function...
July 31, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28751426/parp2-deficiency-affects-invariant-nkt-cell-maturation-and-protects-mice-from-concanavalin-a-induced-liver-injury
#16
Aveline Filliol, Claire Piquet-Pellorce, Sarah Dion, Valentine Genet, Catherine Lucas-Clerc, Françoise Dantzer, Michel Samson
Excessive or persistent inflammation and hepatocyte death are the key triggers of liver diseases. The poly(ADP-ribose) polymerase (PARP) proteins induce cell death and inflammation. Chemical inhibition of PARP activity protects against liver injury during Concanavalin A (ConA)-induced hepatitis. In this mice model, ConA activates immune cells which promote inflammation and induce hepatocyte death, mediated by the activated invariant NKT-(iNKT) lymphocyte population. We analyzed immune cell populations in the liver and several lymphoid organs such as spleen, thymus, and bone marrow in Parp2 deficient mice to better define the role of PARP proteins in liver immunity and inflammation at steady state and during ConA-induced hepatitis...
July 27, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28743554/solubilization-of-%C3%AE-galactosylceramide-in-aqueous-medium-impact-on-natural-killer-t-cell-activation-and-antitumor-responses
#17
Elodie Macho-Fernandez, Neila Chekkat, Christophe Ehret, Jean-Sébastien Thomann, Marcella De Giorgi, Maria Vittoria Spanedda, Line Bourel-Bonnet, Didier Betbeder, Béatrice Heurtault, Christelle Faveeuw, Sylvie Fournel, Benoît Frisch, François Trottein
The potent antitumor effect of α-galactosylceramide (α-GalCer) is based on its recognition by invariant Natural Killer T cells (iNKT) after its capture and presentation by antigen presenting cells including dendritic cells (DCs). Synthetic α-GalCer has already been tested in advanced cancer patients but no or only moderate clinical responses were obtained. To optimize α-GalCer efficacy, we have postulated that alternative formulations impacting its molecular organization in aqueous medium could modify DC uptake and iNKT-based immune responses...
July 22, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28724935/histone-deacetylase-3-is-required-for-inkt-cell-development
#18
Puspa Thapa, Sinibaldo Romero Arocha, Ji Young Chung, Derek B Sant'Angelo, Virginia Smith Shapiro
NKT cells are a distinct subset that have developmental requirements that often differ from conventional T cells. Here, we show that NKT-specific deletion of Hdac3 results in a severe reduction in the number of iNKT cells, particularly of NKT1 cells. In addition, there is decreased cytokine production by Hdac3-deficient NKT2 and NKT17 cells. Hdac3-deficient iNKT cells have increased cell death that is not rescued by transgenic expression of Bcl-2 or Bcl-xL. Hdac3-deficient iNKT cells have less Cyto-ID staining and lower LC3A/B expression, indicative of reduced autophagy...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28723564/the-lysine-acetyltransferase-gcn5-is-required-for-inkt-cell-development-through-egr2-acetylation
#19
Yajun Wang, Chawon Yun, Beixue Gao, Yuanming Xu, Yana Zhang, Yiming Wang, Qingfei Kong, Fang Zhao, Chyung-Ru Wang, Sharon Y R Dent, Jian Wang, Xiangping Xu, Hua-Bin Li, Deyu Fang
The development of CD1d-restricted invariant natural killer T (iNKT) cells, a population that is critical for both innate and adaptive immunity, is regulated by multiple transcription factors, but the molecular mechanisms underlying how the transcriptional activation of these factors are regulated during iNKT development remain largely unknown. We found that the histone acetyltransferase general control non-derepressible 5 (GCN5) is essential for iNKT cell development during the maturation stage. GCN5 deficiency blocked iNKT cell development in a cell-intrinsic manner...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28716901/structural-determination-of-lipid-antigens-captured-at-the-cd1d-t-cell-receptor-interface
#20
Patrick J Brennan, Tan-Yun Cheng, Daniel G Pellicci, Gerald F M Watts, Natacha Veerapen, David C Young, Jamie Rossjohn, Gurdyal S Besra, Dale I Godfrey, Michael B Brenner, D Branch Moody
Glycolipid antigens recognized by αβ T-cell receptors (TCRs) drive the activation of invariant natural killer T (iNKT) cells, a specialized subset of innate T lymphocytes. Glycolipids with α-linked anomeric carbohydrates have been identified as potent microbial lipid antigens for iNKT cells, and their unusual α-anomeric linkage has been thought to define a "foreign" lipid antigen motif. However, mammals use endogenous lipids to select iNKT cells, and there is compelling evidence for iNKT cell responses in various types of sterile inflammation...
August 1, 2017: Proceedings of the National Academy of Sciences of the United States of America
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