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https://www.readbyqxmd.com/read/28436935/tnf-superfamily-receptor-ox40-triggers-invariant-nkt-cell-pyroptosis-and-liver-injury
#1
Peixiang Lan, Yihui Fan, Yue Zhao, Xiaohua Lou, Howard P Monsour, Xiaolong Zhang, Yongwon Choi, Yaling Dou, Naoto Ishii, Rafik M Ghobrial, Xiang Xiao, Xian Chang Li
Tissue-resident immune cells play a key role in local and systemic immune responses. The liver, in particular, hosts a large number of invariant natural killer T (iNKT) cells, which are involved in diverse immune responses. However, the mechanisms that regulate survival and homeostasis of liver iNKT cells are poorly defined. Here we have found that liver iNKT cells constitutively express the costimulatory TNF superfamily receptor OX40 and that OX40 stimulation results in massive pyroptotic death of iNKT cells, characterized by the release of potent proinflammatory cytokines that induce liver injury...
April 24, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28419443/loss-of-natural-killer-t-nkt-cells-promotes-pancreatic-cancer-in-lsl-kras-g12d-mice
#2
Naveena B Janakiram, Altaf Mohammed, Taylor Bryant, Rebekah Ritchie, Nicole Stratton, Lydgia Jackson, Stan Lightfoot, Doris M Benbrook, Adam Asch, Mark L Lang, Chinthalapally V Rao
Role of unique T cell population, Natural Killer T (NKT) cells which have similar functions like NK cells in PC is not yet evaluated. In order to address the regulatory roles of NKT cells on tumor progression through tumor-associated macrophages (TAM) and their production of microsomal prostaglandin E synthase-1 (mPGES-1) and 5-lipoxygenase (5-LOX) in (Kras)-driven pancreatic tumor (KPT) progression, we crossed CD1d(-/-) mice deficient in both iNKT and vNKT cells with the Kras(G12D) mice. Loss of NKT cells significantly increased pancreatic intraepithelial neoplasia lesions [PanINs] and also increased 5-LOX and mPGES-1 expressions in M2 type macrophages and cancer stem like cells in pancreatic tumors...
April 18, 2017: Immunology
https://www.readbyqxmd.com/read/28416503/invariant-natural-killer-t-cells-ameliorate-murine-chronic-gvhd-by-expanding-donor-regulatory-t-cells
#3
Jing Du, Katelyn Paz, Govindarajan Thangavelu, Dominik Schneidawind, Jeanette Baker, Ryan Flynn, Omar Duramad, Colby Feser, Angela Panoskaltsis-Mortari, Robert S Negrin, Bruce R Blazar
Chronic graft-versus-host-disease (cGVHD) can cause multi-organ system disease typically with autoimmune-like features, resulting in high mortality and morbidity due to treatment limitations. Invariant natural killer T cells (iNKTs), a small population characterized by expression of a semi-invariant T-cell receptor, rapidly produce copious amounts of diverse cytokines upon activation that exert potent immune regulatory function. Here, we show that iNKTs are significantly reduced in a cGVHD murine model that recapitulates several aspects of autoimmunity and organ fibrosis observed in cGVHD patients...
April 17, 2017: Blood
https://www.readbyqxmd.com/read/28401935/unique-invariant-natural-killer-t-cells-promote-intestinal-polyps-by-suppressing-th1-immunity-and-promoting-regulatory-t-cells
#4
Y Wang, S Sedimbi, L Löfbom, A K Singh, S A Porcelli, S L Cardell
CD1d-restricted invariant natural killer T (iNKT) cells are known as potent early regulatory cells of immune responses. Besides the established roles in the regulation of inflammation and autoimmune disease, studies have shown that iNKT cells have important roles in tumor surveillance and the control of tumor metastasis. Here we found that the absence of iNKT cells markedly decreased the total number of intestinal polyps in APC(Min/+) mice, a model for colorectal cancer. Polyp iNKT cells were enriched for interleukin-10 (IL-10)- and IL-17-producing cells, showed a distinct phenotype being CD4(+), NK1...
April 12, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28396665/negative-checkpoint-regulatory-molecule-2b4-cd244-upregulation-is-associated-with-invariant-natural-killer-t-cell-alterations-and-human-immunodeficiency-virus-disease-progression
#5
Fareed Ahmad, Esaki M Shankar, Yean K Yong, Hong Y Tan, Gerrit Ahrenstorf, Roland Jacobs, Marie Larsson, Reinhold E Schmidt, Adeeba Kamarulzaman, Abdul W Ansari
The CD1d-restricted invariant natural killer T (iNKT) cells are implicated in innate immune responses against human immunodeficiency virus (HIV). However, the determinants of cellular dysfunction across the iNKT cells subsets are seldom defined in HIV disease. Herein, we provide evidence for the involvement of the negative checkpoint regulator (NCR) 2B4 in iNKT cell alteration in a well-defined cohort of HIV-seropositive anti-retroviral therapy (ART) naïve, ART-treated, and elite controllers (ECs). We report on exaggerated 2B4 expression on iNKT cells of HIV-infected treatment-naïve individuals...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28396661/phenotype-of-nk-like-cd8-t-cells-with-innate-features-in-humans-and-their-relevance-in-cancer-diseases
#6
Alice Barbarin, Emilie Cayssials, Florence Jacomet, Nicolas Gonzalo Nunez, Sara Basbous, Lucie Lefèvre, Myriam Abdallah, Nathalie Piccirilli, Benjamin Morin, Vincent Lavoue, Véronique Catros, Eliane Piaggio, André Herbelin, Jean-Marc Gombert
Unconventional T cells are defined by their capacity to respond to signals other than the well-known complex of peptides and major histocompatibility complex proteins. Among the burgeoning family of unconventional T cells, innate-like CD8(+) T cells in the mouse were discovered in the early 2000s. This subset of CD8(+) T cells bears a memory phenotype without having encountered a foreign antigen and can respond to innate-like IL-12 + IL-18 stimulation. Although the concept of innate memory CD8(+) T cells is now well established in mice, whether an equivalent memory NK-like T-cell population exists in humans remains under debate...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28373584/invariant-nkt-cell-activation-is-potentiated-by-homotypic-trans-ly108-interactions
#7
Yuriy Baglaenko, Mayra Cruz Tleugabulova, Eric Gracey, Nafiseh Talaei, Kieran Patricia Manion, Nan-Hua Chang, Dario Michael Ferri, Thierry Mallevaey, Joan E Wither
Invariant NKT (iNKT) cells are innate lymphocytes that respond to glycolipids presented by the MHC class Ib molecule CD1d and are rapidly activated to produce large quantities of cytokines and chemokines. iNKT cell development uniquely depends on interactions between double-positive thymocytes that provide key homotypic interactions between signaling lymphocyte activation molecule (SLAM) family members. However, the role of SLAM receptors in the differentiation of iNKT cell effector subsets and activation has not been explored...
April 3, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28373486/diastereomer-specific-quantification-of-bioactive-hexosylceramides-from-bacteria-and-mammals
#8
Johanna von Gerichten, Kerstin Schlosser, Dominic Lamprecht, Ivan Morace, Matthias Eckhardt, Dagmar Wachten, Richard Jennemann, Hermann-Josef Gröne, Matthias Mack, Roger Sandhoff
Mammals synthesize cell-type specifically the diastereomeric hexosylceramides β-galactosylceramide (β-GalCer) and β-glucosylceramide (β-GlcCer), which are involved in several diseases such as sphingolipidosis, diabetes, chronic kidney diseases, or cancer. In contrast Bacteroides fragilis, a member of the human gut microbiome, and the marine sponge Agelas mauritianus produce α-galactosylceramide (α-GalCer), one of the most potent stimulators for iNKT cells. To dissect the contribution of these individual stereoisomers to pathologies, we established a novel HILIC based LC MS(2) method and separate (R > 1...
April 3, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28369855/in-vivo-activation-of-invariant-natural-killer-t-cells-induces-systemic-and-local-alterations-in-t-cell-subsets-prior-to-preterm-birth
#9
Nardhy Gomez-Lopez, Roberto Romero, Marcia Arenas-Hernandez, George Schwenkel, Derek St Louis, Sonia S Hassan, Tara N Mial
Preterm birth, the leading cause of neonatal morbidity and mortality worldwide, is frequently preceded by spontaneous preterm labor, a syndrome of multiple etiologies. Pathological inflammation is causally linked to spontaneous preterm labor. Indeed, direct activation of invariant natural killer T (iNKT) cells via α-galactosylceramide induces preterm labor/birth largely by initiating systemic and local (i.e., decidua and myometrium) innate immune responses. Herein, we investigated whether iNKT-cell activation altered local and systemic T-cell subsets...
April 2, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28369682/characterization-and-functional-analysis-of-mouse-semi-invariant-natural-t-cells
#10
Amrendra Kumar, Jelena S Bezbradica, Aleksandar K Stanic, Sebastian Joyce
Semi-invariant natural killer T (iNKT) cells are CD1d-restricted innate-like lymphocytes that recognize lipid agonists. Activated iNKT cells have immunoregulatory properties. Human and mouse iNKT cell functions elicited by different glycolipid agonists are highly conserved, making the mouse an excellent animal model for understanding iNKT cell biology in vivo. This unit describes basic methods for the characterization and quantification (see Basic Protocol 1) and functional analysis of mouse iNKT cells in vivo or in vitro...
April 3, 2017: Current Protocols in Immunology
https://www.readbyqxmd.com/read/28365448/synthesis-and-biological-activities-of-c-glycosides-of-krn-7000-with-novel-ceramide-residues
#11
Ahmad S Altiti, Xiaojing Ma, Lixing Zhang, Yi Ban, Richard W Franck, David R Mootoo
The identification of immunoactive agents for clinical and mechanistic applications is a very active area of research. In this vein, analogues of the potent immunostimulant KRN 7000 with diverse cytokine profiles have attracted considerable attention. These compounds have been shown to activate iNKT cells via presentation by CD1d. Herein, we report on the synthesis and activity for four new C-glycosides of KRN 7000, 11-phenylundecanoyl and 11-p-fluorophenylundecanoyl derivatives of C-KRN 7000, 2,3-bis-epi-C-KRN 7000 and the reverse amide of C-KRN 7000...
March 6, 2017: Carbohydrate Research
https://www.readbyqxmd.com/read/28365328/comparison-of-6b11-mab-and-%C3%AE-galcer-loaded-cd1d-dextramers-for-detection-of-inkt-cells-by-flow-cytometry
#12
Marzena Lenart, Anna Gruca, Anna Mueck, Magdalena Rutkowska-Zapała, Marta Surman, Anna Szaflarska, Krzysztof Kobylarz, Jarosław Baran, Maciej Siedlar
Invariant natural killer T (iNKT) cells are a small population of thymus-derived T cells that are restricted by non-classical MHC class I molecule CD1d and express an evolutionary conserved TCR with an invariant α-chain. The frequency of iNKT cells in peripheral blood is very low, thus, accurate methods to identify and enumerate iNKT cells are needed. The aim of the study was to compare 6B11 mAb or α-GalCer-loaded CD1d dextramers usage in iNKT cell detection. The frequency of CD3(+)CD56(+) lymphocytes is much higher, with statistical significance (p<0,001), than real iNKT cells detected by 6B11 mAb or α-GalCer-loaded CD1d dextramers...
March 30, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28351935/bidirectional-immune-tolerance-in-non-myeloablative-mhc-mismatched-bmt-for-murine-%C3%AE-thalassemia
#13
Shuyu E, Aman Seth, Peter Vogel, Matt Sommers, Taren Ong, Asha B Pillai
Non-myeloablative conditioning using total lymphoid irradiation (TLI) and rabbit anti-thymocyte serum (ATS) (the murine pre-clinical equivalent of anti-thymocyte globulin/ATG) facilitates immune tolerance after bone marrow transplantation (BMT) across major histocompatibility complex (MHC) disparities and may be a useful strategy for non-malignant disorders. We previously reported that donor effector T cell function and GVHD are regulated via recipient invariant natural killer T cell (iNKT cell) IL-4-driven expansion of donor Foxp3(+) naturally occurring Treg...
March 28, 2017: Blood
https://www.readbyqxmd.com/read/28335781/tailored-design-of-nkt-stimulatory-glycolipids-for-polarization-of-immune-responses
#14
REVIEW
Jung-Tung Hung, Jing-Rong Huang, Alice L Yu
Natural killer T (NKT) cell is a distinct population of T lymphocytes that can rapidly release massive amount of Th1 and Th2 cytokines upon the engagement of their T cell receptor with glycolipids presented by CD1d. The secreted cytokines can promote cell-mediated immunity to kill tumor cells and intracellular pathogens, or suppress autoreactive immune cells in autoimmune diseases. Thus, NKT cell is an attractive target for developing new therapeutics to manipulate immune system. The best-known glycolipid to activate NKT cells is α-galactosylceramide (α-GalCer), which has been used as a prototype for designing new NKT stimulatory glycolipids...
March 23, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28322093/peripheral-invariant-natural-killer-t-cell-deficiency-in-metabolically-unhealthy-but-normal-weight-versus-metabolically-healthy-but-obese-individuals
#15
Xiao-Li Wang, Xiang-Yun Chang, Xiao-Xiao Tang, Zhi-Gang Chen, Ting Zhou, Kan Sun
Objective To investigate the proportion of circulating invariant natural killer T (iNKT) cells in four body health types. Methods In this cross-sectional study, participants were classified into four body health types according to the body mass index and metabolic status: metabolically healthy and normal weight (MHNW), metabolically unhealthy but normal weight (MUNW), metabolically healthy but obese (MHO), or metabolically unhealthy and obese (MUO). Demographic and clinical characteristics were measured, and the homeostasis model assessment of insulin resistance (HOMA-IR) and visceral adiposity index (VAI) were calculated...
December 2016: Journal of International Medical Research
https://www.readbyqxmd.com/read/28296542/the-autophagy-machinery-restrains-inkt-cell-activation-through-cd1d1-internalization
#16
Christian W Keller, Monica Loi, Svenja Ewert, Isaak Quast, Romina Theiler, Monique Gannagé, Christian Münz, Gennaro De Libero, Stefan Freigang, Jan D Lünemann
Invariant natural killer T (iNKT) cells are innate T cells with powerful immune regulatory functions that recognize glycolipid antigens presented by the CD1D protein. While iNKT cell-activating glycolipids are currently being explored for their efficacy to improve immunotherapy against infectious diseases and cancer, little is known about the mechanisms that control CD1D antigen presentation and iNKT cell activation in vivo. CD1D molecules survey endocytic pathways to bind lipid antigens in MHC class II-containing compartments (MIICs) before recycling to the plasma membrane...
March 15, 2017: Autophagy
https://www.readbyqxmd.com/read/28295259/applying-the-tor-c-que-in-inkt-cells-a-new-twist-in-an-old-tale
#17
Mihalis Verykokakis, Barbara L Kee
The mammalian Target of Rapamycin (mTOR) protein controls the machinery necessary for T-cell activation, differentiation, and memory formation, as a component of mTOR complex 1 (mTORC1) and mTORC2, which function both downstream and upstream of AKT. Invariant natural killer T (iNKT) cells are a unique T-cell subset that exist in a primed state, capable of rapid activation, and produce large quantities of cytokines. iNKT-cell effector differentiation is dependent on the mTORC1 complex; however, the requirements for mTORC2 in iNKT cells have been controversial...
March 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28294313/suppression-of-murine-tumour-growth-through-cd8-cytotoxic-t-lymphocytes-via-activated-dec-205-dendritic-cells-by-sequential-administration-of-%C3%AE-galactosylceramide-in-vivo
#18
Hideki Kogo, Masumi Shimizu, Yasuyuki Negishi, Eiji Uchida, Hidemi Takahashi
Cancer immunity is mediated through the effective priming and activation of tumour-specific class I MHC molecule-restricted CD8(+) cytotoxic T lymphocytes (CTLs). DEC-205(+) dendritic cells (DCs) can cross-present the epitope(s) of captured tumour antigens associated with class I MHC molecules alongside co-stimulatory molecules to prime and activate tumour-specific CD8(+) CTLs. Immunosuppressive tolerogenic DCs with reduced co-stimulatory molecules may be a cause of impaired CTL induction. Hepa1-6-1 cells were established from the mouse hepatoma cell line Hepa1-6; these cells grow continuously after subcutaneous implantation into syngeneic C57BL/6 (B6) mice and do not prime CD8(+) CTLs...
March 12, 2017: Immunology
https://www.readbyqxmd.com/read/28276165/distribution-of-invariant-natural-killer-t-cells-and-dendritic-cells-in-late-pre-term-birth-without-acute-chorioamnionitis
#19
Yasuyuki Negishi, Yoshio Shima, Toshiyuki Takeshita, Hidemi Takahashi
PROBLEM: Acute chorioamnionitis (aCAM) is an important cause of pre-term birth. However, little is known about the pathogenesis of late pre-term birth without aCAM that was the most common category of pre-term birth. Here we analyze the kinetics of immune cells obtained from the decidua of women with late pre-term births with and without aCAM. METHOD OF STUDY: Deciduas were obtained from women who underwent labor with late pre-term birth without aCAM (PB-n/aCAM) or with aCAM (PB-w/aCAM)...
March 9, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28258199/id2-collaborates-with-id3-to-suppress-invariant-nkt-and-innate-like-tumors
#20
Jia Li, Sumedha Roy, Young-Mi Kim, Shibo Li, Baojun Zhang, Cassandra Love, Anupama Reddy, Deepthi Rajagopalan, Sandeep Dave, Anna Mae Diehl, Yuan Zhuang
Inhibitor of DNA binding (Id) proteins, including Id1-4, are transcriptional regulators involved in promoting cell proliferation and survival in various cell types. Although upregulation of Id proteins is associated with a broad spectrum of tumors, recent studies have identified that Id3 plays a tumor-suppressor role in the development of Burkitt's lymphoma in humans and hepatosplenic T cell lymphomas in mice. In this article, we report rapid lymphoma development in Id2/Id3 double-knockout mice that is caused by unchecked expansion of invariant NKT (iNKT) cells or a unique subset of innate-like CD1d-independent T cells...
April 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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