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https://www.readbyqxmd.com/read/28419443/loss-of-natural-killer-t-nkt-cells-promotes-pancreatic-cancer-in-lsl-kras-g12d-mice
#1
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/28401935/unique-invariant-natural-killer-t-cells-promote-intestinal-polyps-by-suppressing-th1-immunity-and-promoting-regulatory-t-cells
#2
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
#3
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/28392574/m2-specific-reduction-of-cd1d-switches-nkt-cell-mediated-immune-responses-and-triggers-metaflammation-in-adipose-tissue
#4
Huimin Zhang, Rufeng Xue, Shasha Zhu, Sicheng Fu, Zuolong Chen, Rongbin Zhou, Zhigang Tian, Li Bai
Metaflammation is responsible for several metabolic syndromes, such as type 2 diabetes. However, the mechanisms by which metabolic disorders trigger metaflammation remain unclear. We identified a cell type-specific downregulation of CD1d expression in M2 macrophages during the progression of obesity prior to the onset of inflammation in visceral adipose tissues. A reduction in CD1d expression influenced the ability of M2 macrophages to present antigens and caused a change in antigen-presenting cells from M2 macrophages to M1 macrophages...
April 10, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28390155/employing-binol-phosphoroselenoyl-chloride-for-selective-inositol-phosphorylation-and-chemical-synthesis-of-glycosyl-inositol-phospholipid-from-entamoeba-histolytica
#5
Toshihiko Aiba, Sae Suehara, Siew-Ling Choy, Yuuki Maekawa, Hannelore Lotter, Toshiaki Murai, Shinsuke Inuki, Koichi Fukase, Yukari Fujimoto
Here we describe the chemical synthesis of glycosyl inositol phospholipids from Entamoeba histolytica. The key feature of this synthesis is a regioselective phosphorylation reaction that occurs via desymmetrization of a myo-inositol derivative with phosphoroselenoyl chloride. We also developed a new protecting group strategy that utilizes allyl and alloc groups to synthesize complex glycolipids bearing unsaturated lipids. These developments provided an efficient synthetic route for various complex inositol phospholipids and their analogues...
April 8, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28389940/circulating-regulatory-b-cell-subsets-in-patients-with-neuromyelitis-optica-spectrum-disorders
#6
Jinming Han, Li Sun, Zhongkun Wang, Xueli Fan, Lifang Wang, Yang-Yang Song, Jie Zhu, Tao Jin
This study analyzed the populations of three different subsets of regulatory B cells (Bregs) in the peripheral blood mononuclear cells (PBMCs) of patients with neuromyelitis optica spectrum disorders (NMOSDs) and explored the relationship between the changes in these subsets of Bregs and the severity of NMOSD. A total of 22 patients with relapsed NMOSDs before treatment were recruited in our study, along with 20 age and gender-matched healthy controls, from May 2015 to March 2016. The percentages and numbers for three different subsets of Bregs including the CD19(+)CD24(hi)CD38(hi), CD19(+)CD24(hi)CD27(+), and CD19(+)CD5(+)CD1d(hi) populations were evaluated in parallel by flow cytometry...
April 7, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28382974/erratum-the-microbiota-maintain-homeostasis-of-liver-resident-%C3%AE-%C3%AE-t-17-cells-in-a-lipid-antigen-cd1d-dependent-manner
#7
Fenglei Li, Xiaolei Hao, Yongyan Chen, Li Bai, Xiang Gao, Zhexiong Lian, Haiming Wei, Rui Sun, Zhigang Tian
No abstract text is available yet for this article.
April 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28373584/invariant-nkt-cell-activation-is-potentiated-by-homotypic-trans-ly108-interactions
#8
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/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/28363745/nkt-cells-in-cardiovascular-diseases
#13
Gijs H M van Puijvelde, Johan Kuiper
Despite life-style advice and the prescription of cholesterol-lowering and anti-thrombotic drugs, cardiovascular diseases are still the leading cause of death worldwide. Therefore, there is an urgent need for new therapeutic strategies focussing on atherosclerosis, the major underlying pathology of cardiovascular diseases characterized by an accumulation of lipids in an inflamed arterial/vessel wall. CD1d-restricted lipid-sensing natural killer T (NKT) cells, bridging the innate and adaptive immunity, and CD1d-expressing antigen-presenting cells are detected in atherosclerotic lesions of mice and humans...
March 28, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28338767/decreased-cd1d-level-is-associated-with-cd86-over-expression-in-b-cells-from-systemic-lupus-erythematosus
#14
Fei Liu, Jianjian Ji, Xiujun Li, Xiaojing Li, Jingjing Xu, Huimin Yue, Shuli Zhao, Hongye Fan, Yayi Hou
The disorder of B cells is one of the hallmarks of systemic lupus erythematosus (SLE). The activation state indicated by CD86 of B cells from SLE is well known, while the defect of regulatory B cells mediated by CD1d is also responsible for the process of SLE. In the present study, we focused on the relationship between B cell activation mediated by CD86 and B cell regulatory function mediated by CD1d. Our results showed that the level of CD1d in B cells was decreased during the early stages of B6.MRLlpr SLE mice and imiquimod-treated (IMQ-treated) mice, while the level of CD86 was significantly increased at the late stage...
March 3, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28337205/high-interferon-%C3%AE-uniquely-in-v%C3%AE-1-t-cells-correlates-with-markers-of-inflammation-and-axonal-damage-in-early-multiple-sclerosis
#15
Avadhesh Kumar Singh, Lenka Novakova, Markus Axelsson, Clas Malmeström, Henrik Zetterberg, Jan Lycke, Susanna L Cardell
We have identified a population of T lymphocytes in peripheral blood, Vδ1 TCRγδ T lymphocytes, which unexpectedly was uniquely expressing high production of interferon-γ in newly diagnosed, untreated multiple sclerosis (MS) patients. IFN-γ production in this population distinctly correlated to parameters of clinical disease activity, inflammation, and neuronal damage. These Vδ1 T lymphocytes belong to a population of innate T lymphocytes that recognize antigen in the context of CD1d/CD1c and which include reactivity to the myelin glycosphingolipid sulfatide...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28335781/tailored-design-of-nkt-stimulatory-glycolipids-for-polarization-of-immune-responses
#16
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/28330461/impaired-liver-regeneration-is-associated-with-reduced-cyclin-b1-in-natural-killer-t-cell-deficient-mice
#17
Ami Ben Ya'acov, Hadar Meir, Lydia Zolotaryova, Yaron Ilan, Eyal Shteyer
BACKGROUND: It has been shown that the proportion of natural killer T cells is markedly elevated during liver regeneration and their activation under different conditions can modulate this process. As natural killer T cells and liver injury are central in liver regeneration, elucidating their role is important. METHODS: The aim of the current study is to explore the role of natural killer T cells in impaired liver regeneration. Concanvalin A was injected 4 days before partial hepatectomy to natural killer T cells- deficient mice or to anti CD1d1-treated mice...
March 23, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/28296542/the-autophagy-machinery-restrains-inkt-cell-activation-through-cd1d1-internalization
#18
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/28296255/breg-dependent-islet-transplant-tolerance-is-also-nk-cell-dependent
#19
Christian Schuetz, Kang Mi Lee, Ryan Scott, Lisa Kojima, Laura Washburn, Liye Liu, Wei-Hui Liu, Haley Tector, Ji Lei, Heidi Yeh, James Kim, James F Markmann
Immunologic tolerance to solid organ and islet cell grafts has been achieved in various rodent models using antibodies directed at CD45RB and Tim-1. We have shown that this form of tolerance depends on regulatory B-cells. To elucidate further the mechanism by which Bregs induce tolerance we investigated the requirement of NK and NKT cells in this model. To do so, hyperglycemic B6, μMT, Beige or CD1d(-/-) mice received Balb/c islet grafts and treatment with the tolerance inducing regimen consisting of anti-CD45RB and anti -TIM1...
March 10, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28265257/regulatory-b-cells-in-seropositive-myasthenia-gravis-versus-healthy-controls
#20
Md Rezaul Karim, Hong-Yan Zhang, Jiang Yuan, Qiang Sun, Yun-Fu Wang
OBJECTIVE: To find out if the failure in immunotolerance of myasthenia gravis (MG) is a possible aspect of deduction in Breg cells and to characterize B cell subsets in MG. METHODS: Flow cytometry detection and enzyme-linked immunosorbent assays in peripheral blood films of 10 MG patients and 10 healthy controls (HCs) were performed after isolation of B cells. The CD19(+)CD5(+)CD1d(+) Breg cells percentages were measured to complement a B cell phenotype assay and frequencies of B cell subsets...
2017: Frontiers in Neurology
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