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https://www.readbyqxmd.com/read/29018445/natural-killer-t-cells-in-cancer-immunotherapy
#1
REVIEW
Shiny Nair, Madhav V Dhodapkar
Natural killer T (NKT) cells are specialized CD1d-restricted T cells that recognize lipid antigens. Following stimulation, NKT cells lead to downstream activation of both innate and adaptive immune cells in the tumor microenvironment. This has impelled the development of NKT cell-targeted immunotherapies for treating cancer. In this review, we provide a brief overview of the stimulatory and regulatory functions of NKT cells in tumor immunity as well as highlight preclinical and clinical studies based on NKT cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28993781/natural-killer-t-cell-targeted-immunotherapy-mediating-long-term-memory-responses-and-strong-antitumor-activity
#2
Nyambayar Dashtsoodol, Tomokuni Shigeura, Takuya Tashiro, Minako Aihara, Toshihiro Chikanishi, Hiromi Okada, Keigo Hanada, Hirokazu Sano, Akihiko Kurogi, Masaru Taniguchi
Current tumor therapies, including immunotherapies, focus on passive eradication or at least reduction of the tumor mass. However, cancer patients quite often suffer from tumor relapse or metastasis after such treatments. To overcome these problems, we have developed a natural killer T (NKT) cell-targeted immunotherapy focusing on active engagement of the patient's immune system, but not directly targeting the tumor cells themselves. NKT cells express an invariant antigen receptor α chain encoded by Trav11 (Vα14)-Traj18 (Jα18) gene segments in mice and TRAV10 (Vα24)-TRAJ18 (Jα18) in humans and recognize glycolipid ligand in conjunction with a monomorphic CD1d molecule...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28985340/genome-wide-mapping-of-large-deletions-and-their-population-genetic-properties-in-dairy-cattle
#3
Md Mesbah-Uddin, Bernt Guldbrandtsen, Terhi Iso-Touru, Johanna Vilkki, Dirk-Jan De Koning, Didier Boichard, Mogens Sandø Lund, Goutam Sahana
Large genomic deletions are potential candidate for loss-of-function, which could be lethal as homozygote. Analysing whole genome data of 175 cattle, we report 8,480 large deletions (199 bp-773 KB) with an overall false discovery rate of 8.8%; 82% of which are novel compared with deletions in the dbVar database. Breakpoint sequence analyses revealed that majority (24 of 29 tested) of the deletions contain microhomology/homology at breakpoint, and therefore, most likely generated by microhomology-mediated end joining...
September 8, 2017: DNA Research: An International Journal for Rapid Publication of Reports on Genes and Genomes
https://www.readbyqxmd.com/read/28962035/immune-cell-and-transcriptomic-analysis-of-the-human-decidua-in-term-and-preterm-parturition
#4
S F Rinaldi, S Makieva, P T Saunders, A G Rossi, J E Norman
STUDY QUESTION: Is labour, both at term and preterm, associated with alterations in decidual lymphocyte densities and widespread changes to the decidual transcriptome? SUMMARY ANSWER: The onset of parturition, both at term and preterm, is associated with widespread gene expression changes in the decidua, many of which are related to inflammatory signalling, but is not associated with changes in the number of any of the decidual lymphocyte populations examined. WHAT IS KNOWN ALREADY: Given its location, directly at the maternal-foetal interface, the decidua is likely to play a pivotal role in the onset of parturition, however, the molecular events occurring in the decidua in association with the onset of labour, both at term and preterm, remain relatively poorly defined...
August 18, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28945950/complexity-and-function-of-nkt-cells-with-potential-application-to-hepatic-transplant-survival
#5
REVIEW
Randle Ware, Vipin Kumar
One of the major innate-like lymphocyte populations enriched in liver consists of Natural Killer T (NKT) cells, which recognize self and foreign lipid antigens presented by the non-polymorphic class I MHC-like molecule CD1d. NKT cells express NK cell markers as well as T cell receptors (TCR) and can be classified into 2 categories: type I NKT cells use a semi-invariant TCR whereas type II NKT cells express diverse but still limited TCRs. An emerging body of evidence points to their opposing roles in inflammation, including ischemic reperfusion injury...
September 25, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28941322/stromal-cell-derived-factor-1-mediates-cardiac-allograft-tolerance-induced-by-human-endometrial-regenerative-cell-based-therapy
#6
Xu Lan, Grace Wang, Xiaoxi Xu, Shanzheng Lu, Xiang Li, Baoren Zhang, Ganggang Shi, Yiming Zhao, Caigan Du, Hao Wang
Endometrial regenerative cells (ERCs) are mesenchymal-like stromal cells, and their therapeutic potential has been tested in the prevention of renal ischemic reperfusion injury, acute liver injury, ulcerative colitis, and immunosuppression. However, their potential in the induction of transplant tolerance has not been investigated. The present study was undertaken to investigate the efficacy of ERCs in inducing cardiac allograft tolerance and the function of stromal cell-derived factor-1 (SDF-1) in the ERC-mediated immunoregulation...
September 23, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28933361/lysosomal-storage-disorders-and-malignancy
#7
REVIEW
Gregory M Pastores, Derralynn A Hughes
Lysosomal storage disorders (LSDs) are infrequent to rare conditions caused by mutations that lead to a disruption in the usual sequential degradation of macromolecules or their transit within the cell. Gaucher disease (GD), a lipidosis, is among the most common LSD, with an estimated incidence of 1 in 40,000 among the Caucasian, non-Jewish population. Studies have indicated an increased frequency of polyclonal and monoclonal gammopathy among patients with GD. It has been shown that two major sphingolipids that accumulate in GD, namely, β-glucosylceramide 22:0 (βGL1-22) and glucosylsphingosine (LGL1), can be recognized by a distinct subset of CD1d-restricted human and murine type II natural killer T (NKT) cells...
February 27, 2017: Diseases (Basel)
https://www.readbyqxmd.com/read/28905187/altered-b-cell-homeostasis-in-patients-with-major-depressive-disorder-and-normalization-of-cd5-surface-expression-on-regulatory-b-cells-in-treatment-responders
#8
Diana Ahmetspahic, Kathrin Schwarte, Oliver Ambrée, Christian Bürger, Vladislava Falcone, Katharina Seiler, Mehrdad Rahbar Kooybaran, Laura Grosse, Fernand Roos, Julia Scheffer, Silke Jörgens, Katja Koelkebeck, Udo Dannlowski, Volker Arolt, Stefanie Scheu, Judith Alferink
Pro-inflammatory activity and cell-mediated immune responses have been widely observed in patients with major depressive disorder (MDD). Besides their well-known function as antibody-producers, B cells play a key role in inflammatory responses by secreting pro- and anti-inflammatory factors. However, homeostasis of specific B cell subsets has not been comprehensively investigated in MDD. In this study, we characterized circulating B cells of distinct developmental steps including transitional, naïve-mature, antigen-experienced switched, and non-switched memory cells, plasmablasts and regulatory B cells by multi-parameter flow cytometry...
September 13, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28898395/endogenous-lipid-antigens-for-invariant-natural-killer-t-cells-hold-the-reins-in-adipose-tissue-homeostasis
#9
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
#10
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 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28878768/natural-igm-and-tlr-agonists-switch-murine-splenic-pan-b-to-regulatory-cells-that-suppress-ischemia-induced-innate-inflammation-via-regulating-nkt-1-cells
#11
Peter I Lobo, Kailo H Schlegel, Amandeep Bajwa, Liping Huang, Mark D Okusa
Natural IgM anti-leukocyte autoantibodies (IgM-ALAs) inhibit inflammation by several mechanisms. Here, we show that pan-B cells and bone marrow-derived dendritic cells (BMDCs) are switched to regulatory cells when pretreated ex vivo with IgM. B cells are also switched to regulatory cells when pretreated ex vivo with CpG but not with LPS. Pre-emptive infusion of such ex vivo induced regulatory cells protects C57BL/6 mice from ischemia-induced acute kidney injury (AKI) via regulation of in vivo NKT-1 cells, which normally amplify the innate inflammatory response to DAMPS released after reperfusion of the ischemic kidney...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28852174/activation-of-invariant-natural-killer-t-cells-stimulated-with-microbial-%C3%AE-mannosyl-glycolipids
#12
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/28844943/the-unknown-aspect-of-baff-inducing-il-35-production-by-a-cd5-cd1d-hi-fc%C3%AE-riib-hi-regulatory-b-cell-subset-in-lupus
#13
Yamin Zhang, Jun Li, Nuoya Zhou, Yi Zhang, Min Wu, Jian Xu, Chen Shen, Xiangjie An, Guanxin Shen, Ming Yang, Chun Zhang, Juan Tao
IL-35 is a critical immunosuppressive cytokine and plays an important role in various autoimmune diseases. The purpose of this study was to determine whether BAFF, a key pathogenic factor in SLE, also a dichotomous regulator for B cell immune responses, has an effect on IL-35-producing regulatory B cells and its underlying mechanisms in lupus. We found that exogenous BAFF could induce IL-35 production by splenic B cells from MRL-Fas(lpr/lpr) mice. BAFF-induced IL-35-producing B cells were mainly from MZ B cell subset and exhibited a CD5(+)CD1d(hi)FcγRIIb(hi) phenotype...
August 24, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28811651/inkt-cells-prevent-obesity-induced-hepatic-steatosis-in-mice-in-a-c-c-chemokine-receptor-7-dependent-manner
#14
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/28798749/enhancement-of-adjuvant-functions-of-natural-killer-t-cells-using-nanovector-delivery-systems-application-in-anticancer-immune-therapy
#15
REVIEW
Reem Ghinnagow, Luis Javier Cruz, Elodie Macho-Fernandez, Christelle Faveeuw, François Trottein
Type I natural killer T (NKT) cells have gained considerable interest in anticancer immune therapy over the last decade. This "innate-like" T lymphocyte subset has the unique ability to recognize foreign and self-derived glycolipid antigens in association with the CD1d molecule expressed by antigen-presenting cells. An important property of these cells is to bridge innate and acquired immune responses. The adjuvant function of NKT cells might be exploited in the clinics. In this review, we discuss the approaches currently being used to target NKT cells for cancer therapy...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28783690/cross-talk-between-inkt-cells-and-monocytes-triggers-an-atheroprotective-immune-response-in-sle-patients-with-asymptomatic-plaque
#16
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
#17
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/28765611/the-differentiation-of-ror-%C3%AE-t-expressing-inkt17-cells-is-orchestrated-by-runx1
#18
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/28756303/four-pathways-of-cd1-antigen-presentation-to-t-cells
#19
REVIEW
D Branch Moody, Rachel N Cotton
CD1a, CD1b, CD1c and CD1d proteins migrate through distinct subcellular compartments of antigen presenting cells and so can be considered to take four separate pathways leading to display of lipid antigens to T cell receptors. This review discusses the intersection of CD1 trafficking and lipid antigen loading mechanisms in cells, highlighting key controversies relating to CD1 gene expression, size mismatches between antigens and CD1 binding clefts and unexpected mechanisms of T cell receptor-based recognition...
June 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28753651/schistosome-egg-antigens-including-the-glycoprotein-ipse-alpha-1-trigger-the-development-of-regulatory-b-cells
#20
Simone Haeberlein, Katja Obieglo, Arifa Ozir-Fazalalikhan, Mathilde A M Chayé, Henrike Veninga, Luciën E P M van der Vlugt, Astrid Voskamp, Louis Boon, Joke M M den Haan, Lotte B Westerhof, Ruud H P Wilbers, Arjen Schots, Gabriele Schramm, Cornelis H Hokke, Hermelijn H Smits
Infection with the helminth Schistosoma (S.) mansoni drives the development of interleukin (IL)-10-producing regulatory B (Breg) cells in mice and man, which have the capacity to reduce experimental allergic airway inflammation and are thus of high therapeutic interest. However, both the involved antigen and cellular mechanisms that drive Breg cell development remain to be elucidated. Therefore, we investigated whether S. mansoni soluble egg antigens (SEA) directly interact with B cells to enhance their regulatory potential, or act indirectly on B cells via SEA-modulated macrophage subsets...
July 2017: PLoS Pathogens
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