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https://www.readbyqxmd.com/read/28223321/a-non-canonical-function-of-ezh2-preserves-immune-homeostasis
#1
Ajithkumar Vasanthakumar, Dakang Xu, Aaron Tl Lun, Andrew J Kueh, Klaas Pjm van Gisbergen, Nadia Iannarella, Xiaofang Li, Liang Yu, Die Wang, Bryan Rg Williams, Stanley Cw Lee, Ian J Majewski, Dale I Godfrey, Gordon K Smyth, Warren S Alexander, Marco J Herold, Axel Kallies, Stephen L Nutt, Rhys S Allan
Enhancer of zeste 2 (Ezh2) mainly methylates lysine 27 of histone-H3 (H3K27me3) as part of the polycomb repressive complex 2 (PRC2) together with Suz12 and Eed. However, Ezh2 can also modify non-histone substrates, although it is unclear whether this mechanism has a role during development. Here, we present evidence for a chromatin-independent role of Ezh2 during T-cell development and immune homeostasis. T-cell-specific depletion of Ezh2 induces a pronounced expansion of natural killer T (NKT) cells, although Ezh2-deficient T cells maintain normal levels of H3K27me3...
February 21, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28219981/the-role-of-natural-killer-t-cells-in-a-mouse-model-with-spontaneous-bile-duct-inflammation
#2
Elisabeth Schrumpf, Xiaojun Jiang, Sebastian Zeissig, Marion J Pollheimer, Jarl Andreas Anmarkrud, Corey Tan, Mark A Exley, Tom H Karlsen, Richard S Blumberg, Espen Melum
Natural killer T (NKT) cells are activated by lipid antigens presented by CD1d molecules and represent a major lymphocyte subset of the liver. NODc3c4 mice spontaneously develop biliary inflammation in extra- and intrahepatic bile ducts. We demonstrated by flow cytometry that invariant NKT (iNKT) cells were more abundant in the thymus, spleen, and liver of NODc3c4 mice compared to NOD mice. iNKT cells in NODc3c4 mice displayed an activated phenotype. Further, NOD and NODCd1d(-/-) mice were irradiated and injected with NODc3c4 bone marrow, and injection of NODc3c4 bone marrow resulted in biliary infiltrates independently of CD1d expression in recipient mice...
February 2017: Physiological Reports
https://www.readbyqxmd.com/read/28212574/the-combined-action-of-mast-cell-chymase-tryptase-and-carboxypeptidase-a3-protects-against-melanoma-colonization-of-the-lung
#3
Mirjana Grujic, Aida Paivandy, Ann-Marie Gustafson, Allan R Thomsen, Helena Öhrvik, Gunnar Pejler
Mast cell secretory granules are densely packed with various bioactive mediators including proteases of chymase, tryptase and CPA3 type. Previous studies have indicated that mast cells can affect the outcome of melanoma but the contribution of the mast cell granule proteases to such effects has not been clear. Here we addressed this issue by assessing mice lacking either the chymase Mcpt4, the tryptase Mcpt6 or carboxypeptidase A3 (Cpa3), as well as mice simultaneously lacking all three proteases, in a model of melanoma dissemination from blood to the lung...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28208073/temporal-regulation-of-wnt-%C3%AE-catenin-signaling-is-important-for-invariant-nkt-cell-development-and-terminal-maturation
#4
Kalyani Pyaram, Jyoti Misra Sen, Cheong-Hee Chang
The Wnt/β-catenin signaling pathway plays important roles during various cellular functions including survival and proliferation of immune cells. The critical role of this pathway in conventional T cell development is established but little is known about its contributions to innate T cell development. In this study, we found that β-catenin level, an indication of the strength of Wnt/β-catenin signaling, is regulated during invariant NKT (iNKT) cell development. β-catenin levels were greatly increased during iNKT cell selection from double positive thymocytes to Stage 0 of iNKT cell development and during subsequent development to Stage 1...
February 13, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28198713/cd1d-restricted-natural-killer-t-cells-are-preserved-in-indian-long-term-non-progressors-ltnps
#5
Dharmendra Singh, Manisha Ghate, Sheela Godbole, Smita Kulkarni, Madhuri Thakar
BACKGROUND: Natural killer T (NKT) cells act as a bridge between innate and adaptive immune responses. Limited information is available regarding the role of NKT cells in the HIV disease progression especially HIV-1 C infection. METHODOLOGY: NKT cells were characterized for their frequency and the activation, aging, exhaustion status and their proliferation ability in 32 long term non progressors (LTNPs), 40 progressors, 18 patients before and after suppressive cART along with 35 HIV-1 negative subjects using multicolor flowcytometry...
February 14, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28195343/galectin-9-diverse-roles-in-hepatic-immune-homeostasis-and-inflammation
#6
REVIEW
Lucy Golden-Mason, Hugo R Rosen
Glycan-binding proteins which include galectins are involved at all stages of immunity and inflammation, ranging from initiation through resolution. Galectin-9 (Gal-9) is highly expressed in the liver and has a wide variety of biological functions in innate and adaptive immunity that are instrumental in the maintenance of hepatic homeostasis. In the setting of viral hepatitis, increased expression of Gal-9 drives the expansion of regulatory T cells and contraction of effector T cells, thereby favoring viral persistence...
February 13, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28193627/adoptive-transfer-of-invariant-nkt-cells-as-immunotherapy-for-advanced-melanoma-a-phase-1-clinical-trial
#7
Mark A Exley, Philip Friedlander, Nadia Alatrakchi, Lianne Vriend, Simon C Yue, Tetsuro Sasada, Wanyong Zang, Yo Mizukami, Justice Clark, David Nemer, Ken LeClair, Christine Canning, Heather Daley, Glenn Dranoff, Anita Giobbie-Hurder, F Stephen Hodi, Jerome Ritz, Steven P Balk
PURPOSE: Invariant NKT cells (iNKT) are innate-like CD1d-restricted T cells with immunoregulatory activity in diseases including cancer. iNKT from advanced cancer patients can have reversible defects including IFNγ production, and iNKT IFNγ production may stratify for survival. Previous clinical trials using iNKT cell activating ligand α-galactosylceramide have shown responses. Therefore, a phase 1 clinical trial was performed of autologous in vitro expanded iNKT cells in stage IIIB-IV melanoma...
February 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28188245/roquin-paralogs-differentially-regulate-functional-nkt-cell-subsets
#8
Christoph Drees, J Christoph Vahl, Sabrina Bortoluzzi, Klaus D Heger, Julius C Fischer, F Thomas Wunderlich, Christian Peschel, Marc Schmidt-Supprian
NKT cells represent a small subset of glycolipid-recognizing T cells that are heavily implicated in human allergic, autoimmune, and malignant diseases. In the thymus, precursor cells recognize self-glycolipids by virtue of their semi-invariant TCR, which triggers NKT cell lineage commitment and maturation. During their development, NKT cells are polarized into the NKT1, NKT2, and NKT17 subsets, defined through their cytokine-secretion patterns and the expression of key transcription factors. However, we have largely ignored how the differentiation into the NKT cell subsets is regulated...
February 10, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28177888/hdac4-is-expressed-on-multiple-t-cell-lineages-but-dispensable-for-their-development-and-function
#9
Queping Liu, Xilin Zhang, Congcong Yin, Xing Chen, Zhenggang Zhang, Stephen Brown, Hongfu Xie, Li Zhou, Qing-Sheng Mi
Histone deacetylation, reciprocally mediated by histone deacetylases (HDAC) and acetyltransferases, represents one major form of post-translational modification. Previous research indicates that HDACs play an essential regulatory role in the development of various immune cells. However, the specific function of individual HDACs remains largely unexplored. HDAC4, a member of class II HDACs, profoundly investigated in the nervous system, while the expression profile and function of HDAC4 in T cells are barely known...
February 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28169232/membrane-bound-versus-soluble-major-histocompatibility-complex-class-i-related-chain-a-and-major-histocompatibility-complex-class-i-related-chain-b-differential-expression-mechanisms-of-tumor-eradication-versus-evasion-and-current-drug-development-strategies
#10
REVIEW
P K Suresh
Major histocompatibility complex Class I-related chain A/chain B (MICA/MICB) is stress-inducible, highly polymorphic ligands whose expression at the transcript level has been detected in all tissues except the central nervous system. However, their restricted protein expression is due to their regulation at the posttranslational level. Its levels are elevated in virally infected and neoplastically transformed cells. Membrane expression of this NKG2DL marks the aberrant cells for elimination by those immune effector cells that express the cognate NKG2D receptor...
October 2016: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28164685/declined-natural-killer-cells-emerging-in-women-with-unexplained-recurrent-spontaneous-abortion-and-further-reducing-after-medical-therapy
#11
Xianghua Lin, Dijin Lin, Jiao Liu, Yunwen Bao, Zhaofan Luo, Junyue Fang, Ying Wang, Mingpeng Zhao, Chaohui Duan
BACKGROUND: As focus grows on reproduction, the issue of Recurrent Spontaneous Abortion (RSA), especially for unexplained reasons (URSA), is grabbing more and more attention in gynecological immunology. We investigated the changes of peripheral lymphocyte subsets focusing on whether they had some relationship with development of URSA. METHODS: The percentage and absolute count of lymphocyte subsets (T cells, Th cells, Ts cells, B cells, NK cells) were simultaneously evaluated by flow cytometry in URSA patients (n = 48) and healthy controls (HC, n = 22)...
November 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28152086/nnktt120-an-anti-inkt-cell-monoclonal-antibody-produces-rapid-and-sustained-inkt-cell-depletion-in-adults-with-sickle-cell-disease
#12
Joshua J Field, Elaine Majerus, Kenneth I Ataga, Elliot P Vichinsky, Robert Schaub, Robert Mashal, David G Nathan
: Invariant NKT (iNKT) cells can be activated to stimulate a broad inflammatory response. In murine models of sickle cell disease (SCD), interruption of iNKT cell activity prevents tissue injury from vaso-occlusion. NKTT120 is an anti-iNKT cell monoclonal antibody that has the potential to rapidly and specifically deplete iNKT cells and, potentially, prevent vaso-occlusion. We conducted an open-label, multi-center, single-ascending-dose study of NKTT120 to determine its pharmacokinetics, pharmacodynamics and safety in steady-state patients with SCD...
2017: PloS One
https://www.readbyqxmd.com/read/28138156/antibody-dependent-cell-cytotoxicity-adcc-immunotherapy-strategies-enhancing-effector-nk-cells
#13
REVIEW
Maria Carmen Ochoa, Luna Minute, Inmaculada Rodriguez, Saray Garasa, Elisabeth Perez-Ruiz, Susana Inogés, Ignacio Melero, Pedro Berraondo
Antibody-dependent cellular cytotoxicity (ADCC) is a set of mechanisms that target cells coated with IgG antibodies of the proper subclasses (IgG1 in the human) to be the prey of cell-to-cell cytolysis executed by immune cells expressing FcRIIIA (CD16A). These effectors include not only NK cells but also other CD16(+) subsets such as monocyte/macrophages, NKT cells or γδ T cells. In cancer therapy, ADCC is exploited by antibodies that selectively recognize proteins on the surface of malignant cells. An approach to enhance antitumor activity is to act on effector cells so they are increased in their numbers or enhanced in their individual (on a cell per cell basis) ADCC performance...
January 31, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28135253/alternative-pathway-for-the-development-of-v%C3%AE-14-nkt-cells-directly-from-cd4-cd8-thymocytes-that-bypasses-the-cd4-cd8-stage
#14
Nyambayar Dashtsoodol, Tomokuni Shigeura, Minako Aihara, Ritsuko Ozawa, Satoshi Kojo, Michishige Harada, Takaho A Endo, Takashi Watanabe, Osamu Ohara, Masaru Taniguchi
Although invariant Vα14(+) natural killer T cells (NKT cells) are thought to be generated from CD4(+)CD8(+) double-positive (DP) thymocytes, the developmental origin of CD4(-)CD8(-) double-negative (DN) NKT cells still remains unresolved. Here we provide definitive genetic evidence obtained, through studies of mice with DP-stage-specific ablation of expression of the gene encoding the recombinase component RAG-2 (Rag2) and by a fate-mapping approach, that supports the proposal of the existence of an alternative developmental pathway through which a fraction of DN NKT cells with strong T-helper-type-1 (TH1)-biased and cytotoxic characteristics develop from late DN-stage thymocytes, bypassing the DP stage...
March 2017: Nature Immunology
https://www.readbyqxmd.com/read/28131881/ageing-is-not-associated-with-an-altered-immune-response-during-trypanosoma-cruzi-infection-ageing-and-trypanosoma-cruzi-infection
#15
Rafaela Pravato Colato, Vânia Brazão, Fabricia Helena Santello, Míriam Paula Alonso Toldo, Gabriel Tavares do Vale, Carlos Renato Tirapelli, Gabriela Pereira-da-Silva, José Clóvis do Prado
The aims of this work were to evaluate the influence of ageing on the magnitude of the immune response in male Wistar rats infected with the Y strain of Trypanosoma cruzi (T. cruzi). Infected young animals displayed enhanced CD4(+) T cells as compared to uninfected counterparts. Ageing also triggered a significant reduction in CD8(+) T cells compared to young and uninfected groups. The percentage of spleen NKT cells was reduced for all groups, regardless of the infection status. Significant decreased B-cells was noted in aged controls and infected animals as compared to young counterparts...
January 25, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28127028/natural-killer-t-cells-in-atherosclerosis
#16
REVIEW
Godfrey S Getz, Catherine A Reardon
Atherosclerosis is a chronic inflammatory disorder that develops in response to hyperlipidaemia. Cells from both the innate and adaptive immune systems contribute to the development of atherosclerotic lesions. The role of natural killer T (NKT) cells in response to microbial pathogens and inflammatory disorders such as atherosclerosis has received increasing attention in the past 10-15 years. Endogenous self-lipid antigens and exogenous lipid antigens, including those on microorganisms can activate NKT cells...
January 27, 2017: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/28122574/natural-killer-t-cells-contribute-to-the-control-of-acute-retroviral-infection
#17
Elisabeth Littwitz-Salomon, Simone Schimmer, Ulf Dittmer
BACKGROUND: Natural killer T cells (NKT cells) play an important role in the immunity against viral infections. They produce cytokines or have direct cytolytic effects that can restrict virus replication. However, the exact function of NKT cells in retroviral immunity is not fully elucidated. Therefore, we analyzed the antiretroviral functions of NKT cells in mice infected with the Friend retrovirus (FV). RESULTS: After FV infection numbers of NKT cells remained unchanged but activation as well as improved effector functions of NKT cells were found...
January 26, 2017: Retrovirology
https://www.readbyqxmd.com/read/28120096/adjuvant-use-of-the-nkt-cell-agonist-alpha-galactosylceramide-leads-to-enhancement-of-m2-based-dna-vaccine-immunogenicity-and-protective-immunity-against-influenza-a-virus
#18
Fatemeh Fotouhi, Mina Shaffifar, Behrokh Farahmand, Sadegh Shirian, Mohsen Saeidi, Alijan Tabarraei, Ali Gorji, Amir Ghaemi
DNA vaccines can induce both humoral and cellular immune responses in animals. However, DNA vaccines suffer from limited vaccine potency due to low immunogenicity. Therefore, different strategies are required for significant improvement of DNA vaccine efficacy such as inclusion of strong adjuvants. The aim of the present study was to investigate the effects of using α-Galactosylceramide (α-GalCer) as an adjuvant to enhance the immune responses induced by a DNA vaccine, encoding influenza A virus matrix protein 2 (M2), against influenza A challenge...
January 24, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28115591/type-ii-nkt-cells-and-their-emerging-role-in-health-and-disease
#19
REVIEW
Madhav V Dhodapkar, Vipin Kumar
NKT cells recognize lipid Ags presented by a class I MHC-like molecule CD1d, a member of the CD1 family. Although most initial studies on NKT cells focused on a subset with semi-invariant TCR termed invariant NKT cells, the majority of CD1d-restricted lipid-reactive human T cells express diverse TCRs and are termed type II NKT cells. These cells constitute a distinct population of circulating and tissue-resident effector T cells with immune-regulatory properties. They react to a growing list of self- as well as non-self-lipid ligands, and share some properties with both invariant NKT and conventional T cells...
February 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28102966/histone-deacetylase-2-is-decreased-in-peripheral-blood-pro-inflammatory-cd8-t-and-nkt-like-lymphocytes-following-lung-transplant
#20
Greg Hodge, Sandra Hodge, Chien-Li Holmes-Liew, Paul N Reynolds, Mark Holmes
BACKGROUND AND OBJECTIVE: Immunosuppression therapy following lung transplantation fails to prevent chronic rejection in many patients, which is associated with lack of suppression of cytotoxic mediators and pro-inflammatory cytokines in peripheral blood T and natural killer T (NKT)-like cells. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) upregulate/downregulate pro-inflammatory gene expression, respectively; however, differences in the activity of these enzymes following lung transplant are unknown...
February 2017: Respirology: Official Journal of the Asian Pacific Society of Respirology
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