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Inkt cells

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Zhen-Kui Wang, Li Xue, Tao Wang, Xiu-Jie Wang, Zhi-Qiang Su
Invariant natural killer T (iNKT) cells are a unique subset of T cells that have been implicated in inflammation, atopy, autoimmunity, infections, and cancer. Although iNKT cells have been extensively studied over the past decade, its role in the pathogenesis of ischemic brain injury is still largely unknown. In our study, we determined whether iNKT cells infiltration occur in a mouse model of permanent cerebral ischemia. C57BL6/J male mice were treated with either alpha-galactosylceramide (α-GalCer) or vehicle control before undergoing permanent middle cerebral artery occlusion (pMCAO)...
October 28, 2016: Neuroscience Letters
Joren Guillaume, Nora Pauwels, Sandrine Aspeslagh, Dirk M Zajonc, Dirk Elewaut, Serge Van Calenbergh
Alpha-galactosyl ceramide (α-GalCer) is a prototypical synthetic ligand of invariant natural killer T (iNKT) cells. Upon presentation by the MHC class I-like molecule CD1d, this glycolipid stimulates iNKT cells to secrete a vast amount of both pro-inflammatory Th1 and anti-inflammatory Th2 cytokines. Recently, we discovered that selected 6″-modified α-GalCer analogues may produce markedly Th1-biased responses due to the formation of either an additional anchor with CD1d or by establishing extra interactions with the T-cell receptor of iNKT cells...
July 1, 2015: Bioorganic & Medicinal Chemistry
Alysia Birkholz, Marek Nemčovič, Esther Dawen Yu, Enrico Girardi, Jing Wang, Archana Khurana, Nora Pauwels, Elisa Farber, Sampada Chitale, Richard W Franck, Moriya Tsuji, Amy Howell, Serge Van Calenbergh, Mitchell Kronenberg, Dirk M Zajonc
The ability of different glycosphingolipids (GSLs) to activate type I natural killer T cells (NKT cells) has been known for 2 decades. The possible therapeutic use of these GSLs has been studied in many ways; however, studies are needed in which the efficacy of promising GSLs is compared under identical conditions. Here, we compare five unique GSLs structurally derived from α-galactosylceramide. We employed biophysical and biological assays, as well as x-ray crystallography to study the impact of the chemical modifications of the antigen on type I NKT cell activation...
July 10, 2015: Journal of Biological Chemistry
Alysia M Birkholz, Enrico Girardi, Gerhard Wingender, Archana Khurana, Jing Wang, Meng Zhao, Sonja Zahner, Petr A Illarionov, Xiangshu Wen, Michelle Li, Weiming Yuan, Steven A Porcelli, Gurdyal S Besra, Dirk M Zajonc, Mitchell Kronenberg
In this article, we characterize a novel Ag for invariant NKT (iNKT) cells capable of producing an especially robust Th1 response. This glycosphingolipid, DB06-1, is similar in chemical structure to the well-studied α-galactosylceramide (αGalCer), with the only change being a single atom: the substitution of a carbonyl oxygen with a sulfur atom. Although DB06-1 is not a more effective Ag in vitro, the small chemical change has a marked impact on the ability of this lipid Ag to stimulate iNKT cells in vivo, with increased IFN-γ production at 24 h compared with αGalCer, increased IL-12, and increased activation of NK cells to produce IFN-γ...
August 1, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
C Marie Dowds, Richard S Blumberg, Sebastian Zeissig
The human host and the intestinal microbiota co-exist in a mutually beneficial relationship, which contributes to host and microbial metabolism as well as maturation of the host's immune system, among many other pathways (Tremaroli and Backhed, 2012; Hooper et al., 2012). At mucosal surfaces, and particularly in the intestine, the commensal microbiota provides 'colonization resistance' to invading pathogens and maintains homeostasis through microbial regulation of mucosal innate and adaptive immunity (Renz et al...
August 2015: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Arun Kannan, YongChan Lee, Qian Qi, Weishan Huang, Ah-Reum Jeong, Sarah Ohnigian, Avery August
Itk(-/-) mice exhibit defects in the activation, development, and function of CD4(+) and CD8(+) T cells and iNKT cells. These and other defects in these mice make it difficult to uncouple the developmental versus functional requirement of Itk signaling. Here, we report an allele-sensitive mutant of Itk (Itkas) whose catalytic activity can be selectively inhibited by analogs of the PP1 kinase inhibitor. We show that Itkas behaves like WT Itk in the absence of the inhibitor and can rescue the development of Itk(-/-) T cells in mice...
August 2015: European Journal of Immunology
Simon Gebremeskel, Daniel R Clattenburg, Drew Slauenwhite, Lynnea Lobert, Brent Johnston
Metastatic lesions are responsible for over 90% of breast cancer associated deaths. Therefore, strategies that target metastasis are of particular interest. This study examined the efficacy of natural killer T (NKT) cell activation as a post-surgical immunotherapy in a mouse model of metastatic breast cancer. Following surgical resection of orthotopic 4T1 mammary carcinoma tumors, BALB/c mice were treated with NKT cell activating glycolipid antigens (α-GalCer, α-C-GalCer or OCH) or α-GalCer-loaded dendritic cells (DCs)...
March 2015: Oncoimmunology
Alysia M Birkholz, Amy R Howell, Mitchell Kronenberg
Glycosphingolipids are a subgroup of glycolipids that contain an amino alcohol sphingoid base linked to sugars. They are found in the membranes of cells ranging from bacteria to vertebrates. This group of lipids is known to stimulate the immune system through activation of a type of white blood cell known as natural killer T cell (NKT cell). Here we summarize the extensive research that has been done to identify the structures of natural glycolipids that stimulate NKT cells and to determine how these antigens are recognized...
June 19, 2015: Journal of Biological Chemistry
Zhen-Min Jiang, Wei Luo, Qian Wen, Su-Dong Liu, Pei-Pei Hao, Chao-Ying Zhou, Ming-Qian Zhou, Li Ma
INTRODUCTION: The invariant natural killer T (iNKT) cell has been shown to play a central role in early stages immune responses against Mycobacterium tuberculosis (Mtb) infection, which become nonresponsive (anergic) and fails to control the growth of Mtb in patients with active tuberculosis. Enhancement of iNKT cell responses to Mtb antigens can help to resist infection. STUDY DESIGN AND METHODS: In the present study, an Mtb 38-kDa antigen-specific T cell receptor (TCR) was isolated from human CD8(+) T cells stimulated by 38-kDa antigen in vitro, and then transduced into primary iNKT cells by retrovirus vector...
2015: Journal of Translational Medicine
Maria Ignez Gaspar-Elsas, Túlio Queto, Daniela Masid-de-Brito, Bruno Marques Vieira, Bianca de Luca, Fernando Queiroz Cunha, Pedro Xavier-Elsas
BACKGROUND AND PURPOSE: α-Galactosylceramide (α-GalCer), a pleiotropic immunomodulator with therapeutic potential in neoplastic, autoimmune and allergic diseases, activates invariant natural killer T-cells throughCD1-restricted receptors for α-GalCer on antigen-presenting cells, inducing cytokine secretion. However the haemopoietic effects of α-GalCer remain little explored. EXPERIMENTAL APPROACH: α-GalCer-induced modulation of eosinophil production in IL-5-stimulated bone marrow cultures was examined in wild-type (BALB/c, C57BL/6) mice and their mutants lacking CD1, inducible NOS (iNOS), CD95 and IFN-γ, along with the effects of lymphocytes; IFN-γ; caspase and iNOS inhibitors; non-steroidal anti-inflammatory drugs (NSAIDs) and LTD4 ; and dexamethasone...
July 2015: British Journal of Pharmacology
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