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Yuke He, Hui Peng, Rui Sun, Haiming Wei, Hans-Gustaf Ljunggren, Wayne M Yokoyama, Zhigang Tian
Engagement of inhibitory receptors by cognate host MHC-I molecules triggers NK cell education, resulting in functional maturation and allowing NK cells to sense missing-self. However, NK cells also express inhibitory receptors for non-MHC-I ligands and their role in NK cell education is poorly understood. TIGIT is a recently identified inhibitory receptor that recognizes a non-MHC-I ligand CD155. Here, we demonstrated that TIGIT(+) NK cells from wild-type mice exerted augmented responsiveness to various stimuli, including targets that lacked expression of CD155 ligand...
April 21, 2017: Journal of Autoimmunity
Wenjie Zhao, Xiaoyang Yue, Kuai Liu, Junfeng Zheng, Runda Huang, Jun Zou, Gabriela Riemekasten, Frank Petersen, Xinhua Yu
Pulmonary fibrosis (PF) is one of the leading causes of death in systemic sclerosis (SSc) patients. Although all SSc patients are characterized by autoimmunity, only part of them suffer from PF, suggesting that beside autoimmunity, some additional factors are involved in the initiation of PF in SSc. In this study, we aimed to identify genetic polymorphisms associated with the status of PF in SSc. We performed that an exhaustive search of the PubMed database was performed to identify eligible studies. Then, a comprehensive meta-analysis was performed by comparing PF(+)-SSc and PF(-)-SSc patients to identify genetic polymorphisms associated with the status of PF in SSc...
April 22, 2017: Rheumatology International
Naomi Takahashi, Makoto Sugaya, Hiraku Suga, Tomonori Oka, Makiko Kawaguchi, Tomomitsu Miyagaki, Hideki Fujita, Takashi Inozume, Shinichi Sato
Immune checkpoint therapy, which targets regulatory pathways in T cells to enhance antitumor immune responses, has led to important clinical advances. CD155 is expressed in various types of cancer and this surface molecule on tumor cells functions either as a co-stimulatory molecule or a co-inhibitory molecule, depending on its receptor. CD226, a CD155 ligand, is mainly expressed on NK cells and CD8(+) T cells, playing important roles in NK cell-mediated cytotoxicity. In this study, we investigated expression and function of CD155 and CD226 in cutaneous T-cell lymphoma (CTCL)...
April 7, 2017: Journal of Investigative Dermatology
William C Dougall, Sema Kurtulus, Mark J Smyth, Ana C Anderson
While therapies targeting the co-inhibitory or immune checkpoint receptors PD-1 and CTLA-4 have shown remarkable success in many cancers, not all patients benefit from these therapies. This has catalyzed enormous interest in the targeting of other immune checkpoint receptors. In this regard, TIGIT and CD96 have recently entered the limelight as novel immune checkpoint receptor targets. TIGIT and CD96 together with the co-stimulatory receptor CD226 form a pathway that is analogous to the CD28/CTLA-4 pathway, in which shared ligands and differential receptor:ligand affinities fine-tune the immune response...
March 2017: Immunological Reviews
Catharina C Gross, Gerd Meyer Zu Hörste, Andreas Schulte-Mecklenbeck, Luisa Klotz, Sven G Meuth, Heinz Wiendl
No abstract text is available yet for this article.
February 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
Baoxing Jia, Ludong Tan, Zhe Jin, Yan Jiao, Yu Fu, Yahui Liu
Our study is aim to investigate the influence of miR-892a on proliferative and invasive activities of human hepatocellular carcinoma (HCC) cells through regulating CD226 expression. QRT-PCR was used to detect the expression levels of miR-892a and CD226 mRNA in HCC tissues and adjacent tissues or HCC cells and normal cells whereas Western Blot was used to detect the CD226 protein expression in tissue and cell samples. Then HuH-7 cell line was selected for following assays and respectively transfected with miR-892a mimics, miR-NC, Plenti-GIII-Ubc-CD226, and Plenti-GIII-Ubc followed by qRT-PCR assay to detect the miR-892a and CD226 expression...
June 2017: Journal of Cellular Biochemistry
Benedetta Pignoloni, Cinzia Fionda, Valentina Dell'Oste, Anna Luganini, Marco Cippitelli, Alessandra Zingoni, Santo Landolfo, Giorgio Gribaudo, Angela Santoni, Cristina Cerboni
Elimination of virus-infected cells by cytotoxic lymphocytes is triggered by activating receptors, among which NKG2D and DNAM-1/CD226 play an important role. Their ligands, that is, MHC class I-related chain (MIC) A/B and UL16-binding proteins (ULBP)1-6 (NKG2D ligand), Nectin-2/CD112, and poliovirus receptor (PVR)/CD155 (DNAM-1 ligand), are often induced on virus-infected cells, although some viruses, including human CMV (HCMV), can block their expression. In this study, we report that infection of different cell types with laboratory or low-passage HCMV strains upregulated MICA, ULBP3, and PVR, with NKG2D and DNAM-1 playing a role in NK cell-mediated lysis of infected cells...
November 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Daqing Nie, Hongbo Li, Guixiu Yan, Zhengyi Wang, Zhaomin He, Wenyu Zhou
The aim of the study is to investigate the impact of CD40 and CD226 gene single-nucleotide polymorphism (SNP) and additional gene-gene interaction on systemic lupus erythematosus (SLE) risk in Chinese Han populations. Three SNPs were selected for genotyping in the case-control study: rs4810485, rs763361, and rs3765456. Logistic regression was performed to investigate association between SNP within CD40 and CD226 and SLE. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the interaction among three SNPs...
December 2016: Rheumatology International
Yun-Peng Peng, Chun-Hua Xi, Yi Zhu, Ling-Di Yin, Ji-Shu Wei, Jing-Jing Zhang, Xin-Chun Liu, Song Guo, Yue Fu, Yi Miao
The progression of pancreatic cancer (PC) is significantly associated with tumor immune escape, which may be associated with nature killer (NK) cell dysfunction. CD226, CD96, and TIGIT, which share the ligand CD155, play important roles in the regulation of NK cell function. The present study was conducted to investigate the roles of these molecules in NK cells from PC patients. Expression of these molecules on NK cells was detected from samples of 92 pancreatic cancer patients and 40 healthy controls. The expression of CD155 was also evaluated by immunohistochemistry in 88 pancreatic cancer tissues...
October 11, 2016: Oncotarget
Matthias Braun, Marie L Ress, Young-Eun Yoo, Claus J Scholz, Matthias Eyrich, Paul G Schlegel, Matthias Wölfl
Interleukin 12 (IL12) is a key inflammatory cytokine critically influencing Th1/Tc1-T-cell responses at the time of initial antigen encounter. Therefore, it may be exploited for cancer immunotherapy. Here, we investigated how IL12, and other inflammatory cytokines, shape effector functions of human T-cells. Using a defined culture system, we followed the gradual differentiation and function of antigen-specific CD8(+) T cells from their initial activation as naïve T cells through their expansion phase as early memory cells to full differentiation as clonally expanded effector T cells...
July 2016: Oncoimmunology
Stephen J Blake, William C Dougall, John J Miles, Michele W L Teng, Mark J Smyth
The receptors CD96 and TIGIT are expressed on the surface of T and natural killer (NK) cells, and recent studies suggest both play important inhibitory roles in immune function. CD96 has been shown to modulate immune cell activity in mice, with Cd96(-)(/)(-) mice displaying hypersensitive NK-cell responses to immune challenge and significant tumor resistance. TIGIT overexpression has been shown to reduce NK-cell-mediated cytotoxicity. TIGIT is also upregulated on T cells during cancer and chronic viral infection, with expression associated with effector T-cell exhaustion and increased regulatory T-cell suppression...
November 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Ki-Wook Kim, Jesse W Williams, Ya-Ting Wang, Stoyan Ivanov, Susan Gilfillan, Marco Colonna, Herbert W Virgin, Emmanuel L Gautier, Gwendalyn J Randolph
Peritoneal and pleural resident macrophages in the mouse share common features and in each compartment exist as two distinct subpopulations: F4/80(+) macrophages and MHC II(+) CD11c(+) macrophages. F4/80(+) macrophages derive from embryonic precursors, and their maintenance is controlled by Gata6. However, the origin and regulatory factors that maintain MHC II(+) macrophages remain unknown. Here, we show that the MHC II(+) macrophages arise postnatally from CCR2-dependent precursors that resemble monocytes...
September 19, 2016: Journal of Experimental Medicine
Zeynep Sener, Fritjof H Cederkvist, Roman Volchenkov, Halvor L Holen, Bjørn S Skålhegg
Immune responses often take place where nutrients and O2 availability are limited. This has an impact on T cell metabolism and influences activation and effector functions. T cell proliferation and expansion are associated with increased consumption of glutamine which is needed in a number of metabolic pathways and regulate various physiological processes. The first step in endogenous glutamine metabolism is reversible and is regulated by glutaminase (GLS1 and GLS2) and glutamine synthase (GLUL). There are two isoforms of GLS1, Kidney type glutaminase (KGA) and Glutaminase C (GAC)...
2016: PloS One
E Myrthianou, M I Zervou, A Budu-Aggrey, E Eliopoulos, D Kardassis, D T Boumpas, N Kougkas, A Barton, P Sidiropoulos, G N Goulielmos
OBJECTIVES: Several rheumatoid arthritis (RA) susceptibility loci have also been found to be associated with psoriatic arthritis (PsA), demonstrating that there is a degree of genetic overlap between various autoimmune diseases. We sought to investigate whether single nucleotide polymorphisms (SNPs) mapping to previously reported RA and/or PsA susceptibility loci, including PLCL2, CCL21, REL, STAT4, CD226, PTPN22, and TYK2, are associated with risk for the two diseases in a genetically homogeneous Greek population...
July 20, 2016: Scandinavian Journal of Rheumatology
Zachary B Davis, Bharatwaj Sowrirajan, Andrew Cogswell, Jeffery P Ward, Vicente Planelles, Edward Barker
Activation of primary CD4(+) T cells induces the CD155, but not the CD112 ligands for the natural killer (NK) cell activation receptor (aNKR) CD226 [DNAX accessory molecule-1 (DNAM-1)]. We hypothesize that HIV productively infects activated CD4(+) T cells and makes itself vulnerable to NK cell-mediated lysis when CD155 on infected T cells engages DNAM-1. The primary objective of this study is to determine whether CD155 alone or together with NKG2D ligands triggers autologous NK cell lysis of HIV-infected T cells and whether HIV modulates CD155...
February 2017: AIDS Research and Human Retroviruses
Minoru Kanaya, Kazuko Shibuya, Rei Hirochika, Miyoko Kanemoto, Kazuteru Ohashi, Masafumi Okada, Yukiko Wagatsuma, Yukiko Cho, Hiroshi Kojima, Takanori Teshima, Masahiro Imamura, Hisashi Sakamaki, Akira Shibuya
Acute graft-versus-host disease (aGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Because diagnosis of aGVHD is exclusively based on clinical symptoms and pathological findings, reliable and noninvasive laboratory tests for accurate diagnosis are required. An activating immunoreceptor, DNAM-1 (CD226), is expressed on T cells and natural killer cells and is involved in the development of aGVHD. Here, we identified a soluble form of DNAM-1 (sDNAM-1) in human sera...
2016: PloS One
Akiko Iguchi-Manaka, Genki Okumura, Hiroshi Kojima, Yukiko Cho, Rei Hirochika, Hiroko Bando, Toyomi Sato, Hiroyuki Yoshikawa, Hisato Hara, Akira Shibuya, Kazuko Shibuya
Emerging evidence suggests that DNAM-1 (CD226) play an important role in the recognition of tumor cells and their lysis by cytotoxic T lymphocytes (CTL) and NK cells. Although the DNAM-1 ligand CD155 is ubiquitously expressed in various tissues, many human tumors significantly upregulate the expression of CD155; DNAM-1 on CTL and NK cells may be involved in tumor immunity. However, unlike those in mice, human tissues also express soluble isoforms of CD155 (sCD155) that lack the transmembrane region. Here, we show that sCD155 levels were significantly higher in the sera of 262 patients with lung, gastrointestinal, breast, and gynecologic cancers than in sera from healthy donors...
2016: PloS One
Laura E Smith, Marcin A Olszewski, Anna-Maria Georgoudaki, Arnika K Wagner, Thomas Hägglöf, Mikael C I Karlsson, Margarita Dominguez-Villar, Francisco Garcia-Cozar, Steffan Mueller, Inga Ravens, Günter Bernhardt, Benedict J Chambers
Previous studies have suggested that NK cells may limit T cell responses by their ability to eradicate dendritic cells, as demonstrated by NK cell-mediated killing of dendritic cells generated from mouse bone marrow cells or human monocytes with GM-CSF. In the present study, we demonstrated that conventional dendritic cells, generated in vitro with Flt3 ligand or from spleens, were resistant to NK cell-mediated lysis. However, upon stimulation with GM-CSF, NK cells could mediate lysis of these dendritic cells...
March 31, 2016: Journal of Leukocyte Biology
Rong Zhang, Hanyu Zeng, Yun Zhang, Kun Chen, Chunmei Zhang, Chaojun Song, Liang Fang, Zhuwei Xu, Kun Yang, Boquan Jin, Qintao Wang, Lihua Chen
Treatment targeting CD226 can ameliorate experimental autoimmune encephalomyelitis (EAE), the widely accepted model of MS. However, the mechanisms still need to be elucidated. Here we showed that CD226 blockage by anti-CD226 blocking mAb LeoA1 efficiently promoted IL-10 production in human peripheral blood monocytes (PBMC) or in mixed lymphocyte culture (MLC) system, significantly induced the CD4+IL-10+ T cell differentiation while suppressing the generation of Th1 and Th17. Furthermore, CD226 pAb administration in vivo reduced the onset of EAE in mice by promoting IL-10 production and regulating T cell differentiation...
April 12, 2016: Oncotarget
Yuan Zhang, Tian Liu, Yu Chen, Zilong Dong, Jinxue Zhang, Yizheng Sun, Boquan Jin, Feng Gao, Shuzhong Guo, Ran Zhuang
CD226 is a co-stimulatory adhesion molecule found on immune and endothelial cells. Here, we evaluated a possible role for CD226 in inhibiting glucose uptake in isolated human umbilical vein endothelial cells (HUVECs) and in wild-type (WT) and CD226 knockout (KO) mice with high-fat diet (HFD)-induced type 2 diabetes (T2DM). CD226 expression increased under hyperglycemic conditions in the presence of TNF-α. Furthermore, CD226 knockdown improved glucose uptake in endothelial cells, and CD226 KO mice exhibited increased glucose tolerance...
March 15, 2016: Oncotarget
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