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https://www.readbyqxmd.com/read/29868026/coming-of-age-cd96-emerges-as-modulator-of-immune-responses
#1
REVIEW
Hristo Georgiev, Inga Ravens, Georgia Papadogianni, Günter Bernhardt
CD96 represents a type I transmembrane glycoprotein belonging to the immunoglobulin superfamily. CD96 is expressed mainly by cells of hematopoietic origin, in particular on T and NK cells. Upon interaction with CD155 present on target cells, CD96 was found to inhibit mouse NK cells, and absence of this interaction either by blocking with antibody or knockout of CD96 showed profound beneficial effects in containment of tumors and metastatic spread in murine model systems. However, our knowledge regarding CD96 functions remains fragmentary...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29721390/cd96-targeted-antibodies-need-not-block-cd96-cd155-interactions-to-promote-nk-cell-anti-metastatic-activity
#2
Amelia Roman Aguilera, Viviana P Lutzky, Deepak Mittal, Xian-Yang Li, Kimberley Stannard, Kazuyoshi Takeda, Günter Bernhardt, Michele W L Teng, William C Dougall, Mark J Smyth
CD96 is a transmembrane glycoprotein Ig superfamily receptor, expressed on various T cell subsets and NK cells, that interacts with nectin and nectin-like proteins, including CD155/polio virus receptor (PVR). Here, we have compared three rat anti-mouse CD96 mAbs, including two that block CD96-CD155 (3.3 and 6A6) and one that does not block CD96-CD155 (8B10). Using flow cytometry, we demonstrated that both mAbs 3.3 and 6A6 bind to the first Ig domain of mouse CD96 and compete with CD155 binding, while mAb 8B10 binds to the second Ig domain and does not block CD155...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29707134/a-jurkat-76-based-triple-parameter-reporter-system-to-evaluate-tcr-functions-and-adoptive-t-cell-strategies
#3
Sandra Rosskopf, Judith Leitner, Wolfgang Paster, Laura T Morton, Renate S Hagedoorn, Peter Steinberger, Mirjam H M Heemskerk
Adoptive T cell therapy using TCR transgenic autologous T cells has shown great potential for the treatment of tumor patients. Thorough characterization of genetically reprogrammed T cells is necessary to optimize treatment success. Here, we describe the generation of triple parameter reporter T cells based on the Jurkat 76 T cell line for the evaluation of TCR and chimeric antigen receptor functions as well as adoptive T cell strategies. This Jurkat subline is devoid of endogenous TCR alpha and TCR beta chains, thereby circumventing the problem of TCR miss-pairing and unexpected specificities...
April 3, 2018: Oncotarget
https://www.readbyqxmd.com/read/29625966/identification-of-st3agl4-mfhas1-csnk2a2-and-cd226-as-loci-associated-with-systemic-lupus-erythematosus-sle-and-evaluation-of-sle-genetics-in-drug-repositioning
#4
Yong-Fei Wang, Yan Zhang, Zhengwei Zhu, Ting-You Wang, David L Morris, Jiangshan Jane Shen, Huoru Zhang, Hai-Feng Pan, Jing Yang, Sen Yang, Dong-Qing Ye, Timothy J Vyse, Yong Cui, Xuejun Zhang, Yujun Sheng, Yu Lung Lau, Wanling Yang
OBJECTIVES: Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with a strong genetic component in its pathogenesis. Through genome-wide association studies (GWAS), we recently identified 10 novel loci associated with SLE and uncovered a number of suggestive loci requiring further validation. This study aimed to validate those loci in independent cohorts and evaluate the role of SLE genetics in drug repositioning. METHODS: We conducted GWAS and replication studies involving 12 280 SLE cases and 18 828 controls, and performed fine-mapping analyses to identify likely causal variants within the newly identified loci...
April 6, 2018: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29550821/blocking-cd226-promotes-allogeneic-transplant-immune-tolerance-and-improves-skin-graft-survival-by-increasing-the-frequency-of-regulatory-t-cells-in-a-murine-model
#5
Tian Liu, Dongliang Zhang, Yuan Zhang, Xiangsheng Xu, Bo Zhou, Liang Fang, Yun Zhang, Yingjun Su, Boquan Jin, Ran Zhuang, Shuzhong Guo
BACKGROUND/AIMS: Regulatory T cells (Tregs) play key roles in maintaining peripheral tolerance and preventing autoimmune disease. Treg modulation could be helpful in treating malignancies, autoimmune disease, and allergies, as well as to facilitate organ transplantation. Signals transduced by co-stimulatory molecules are essential for Treg differentiation, homeostasis, and function. One well-known active receptor, CD226, also known as DNAM-1 or PTA1, is an adhesion molecule that interacts primarily with CD155 and is involved in Treg differentiation and immune tolerance to transplanted tissue...
2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29392336/an-il-15-superagonist-il-15r%C3%AE-fusion-complex-protects-and-rescues-nk-cell-cytotoxic-function-from-tgf-%C3%AE-1-mediated-immunosuppression
#6
Rika Fujii, Caroline Jochems, Sarah R Tritsch, Hing C Wong, Jeffrey Schlom, James W Hodge
Natural killer (NK) cells are innate cytotoxic lymphocytes that play a fundamental role in the immunosurveillance of cancers. NK cells of cancer patients exhibit impaired function mediated by immunosuppressive factors released from the tumor microenvironment (TME), such as transforming growth factor (TGF)-β1. An interleukin (IL)-15 superagonist/IL-15 receptor α fusion complex (IL-15SA/IL-15RA; ALT-803) activates the IL-15 receptor on CD8 T cells and NK cells, and has shown significant anti-tumor activity in several in vivo studies...
April 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29380244/immunological-impact-of-wharton-s-jelly-mesenchymal-stromal-cells-and-natural-killer-cell-co-culture
#7
Mehdi Najar, Mohammad Fayyad-Kazan, Nathalie Meuleman, Dominique Bron, Hussein Fayyad-Kazan, Laurence Lagneaux
Due to their easier isolation, multilineage potential, and immunomodulatory capacity, Wharton's Jelly-derived mesenchymal stromal cells (WJ-MSCs) exhibit promising efficacy in the field of regenerative medicine and immunotherapy. Characterization of WJ-MSCs-natural killer (NK) cells crosstalk is required for ameliorating the medicinal value of WJ-MSCs. Here, we revealed that the outcome of WJ-MSCs-NK cells crosstalk varied according to the type of cytokines (IL-2, IL-12, IL-15 and IL-21) utilized to activate NK cells...
January 30, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29349889/t-cell-immunoglobulin-and-itim-domain-contributes-to-cd8-t-cell-immunosenescence
#8
Yangzi Song, Beibei Wang, Rui Song, Yu Hao, Di Wang, Yuxin Li, Yu Jiang, Ling Xu, Yaluan Ma, Hong Zheng, Yaxian Kong, Hui Zeng
Aging is associated with immune dysfunction, especially T-cell defects, which result in increased susceptibility to various diseases. Previous studies showed that T cells from aged mice express multiple inhibitory receptors, providing evidence of the relationship between T-cell exhaustion and T-cell senescence. In this study, we showed that T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT), a novel co-inhibitory receptor, was upregulated in CD8+ T cells of elderly adults...
April 2018: Aging Cell
https://www.readbyqxmd.com/read/29338153/association-study-of-cd226-and-cd247-genes-single-nucleotide-polymorphisms-in-iranian-patients-with-systemic-sclerosis
#9
Fatemeh Abbasi, Reza Mansouri, Farhad Gharibdoost, Saeed Aslani, Shayan Mostafaei, Hoda Kavosi, Shiva Poursani, Soheila Sobhani, Mahdi Mahmoudi
CD247 and CD226 play important roles in signaling of lymphocytes. Single nucleotide polymorphisms (SNPs) of genes encoding CD247 and CD226 have been associated with the risk of several autoimmune disorders. This study aimed to evaluate the possible association between CD226 and CD247 genes SNPs and risk of systemic sclerosis (SSc) in Iranian population. Study participants were 455 SSc patients and 455 age, sex and ethnic -matched healthy individuals. Genotyping of rs2056626 and rs763361 at CD247 and CD226 genes, respectively, was carried out using TaqMan MGB-based allelic discrimination real-time PCR...
December 2017: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/29319370/association-between-cd226-polymorphism-and-soluble-levels-in-rheumatoid-arthritis-relationship-with-clinical-activity
#10
Youssef M Mosaad, Ehab Es El-Toraby, Ziyad Me Tawhid, Adel I Abdelsalam, Asmaa F Enin, Amany Me Hasson, Ghada M Shafeek
OBJECTIVE: To study the relation between CD226 rs763361 gene polymorphism and CD226 serum level and to evaluate their role in susceptibility and disease activity of RA in a cohort of Egyptian individuals. METHODS: The serum level of CD226 was measured using a suitable ELISA kit and the CD226 rs763361 gene polymorphism was typed by PCR-RFLP for 112 RA patients and 100 healthy controls. RESULTS: Significant association with RA was found with CD226 T allele (OR (95%CI) = 1...
April 2018: Immunological Investigations
https://www.readbyqxmd.com/read/29299389/cd226-deficiency-improves-cognitive-functions-and-ameliorates-anxiety-like-behaviors-in-mice
#11
Liang Fang, Jingyi Jin, Ping Chen, Ning Wang, Hanyu Zeng, Boquan Jin, Hui Li, Lihua Chen
Background: CD226 is a cell surface adhesion molecule expressed in the immune system and central nervous system. Although the role of CD226 in the function of immune cells has been well studied, there has been no report on the potential functional significance of CD226 in neural cells. Methods: We investigated the role of CD226 on the cognitive function and behaviors using CD226 knockout (CD226KO) and wild-type mice. The spatial learning and memory were characterized using Morris water maze test, and the behaviors were evaluated using open field and elevated plus maze tests...
December 2017: Brain and Behavior
https://www.readbyqxmd.com/read/29220498/nkg2c-deletion-is-a-risk-factor-for-human-cytomegalovirus-viremia-and-disease-after-lung-transplantation
#12
Hannes Vietzen, Karin Pollak, Claudia Honsig, Peter Jaksch, Elisabeth Puchhammer-Stöckl
Human cytomegalovirus (HCMV) replication is limited by HCMV-specific natural killer (NK) cell response. Distinct genetic polymorphisms, which are potentially involved in antiviral NK cell response, have been described. Here, the association between polymorphisms at IgG1 genetic marker 3/17, FcγRIIIα/CD16a 158V/F, NKG2Cwt/del, CD226/rs727088, and rs763361, respectively, and HCMV viremia and disease were investigated in 98 lung transplant recipients (LTRs), within 9 months after stop of posttransplant HCMV prophylaxis...
February 14, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29217528/t-cells-expressing-checkpoint-receptor-tigit-are-enriched-in-follicular-lymphoma-tumors-and-characterized-by-reversible-suppression-of-t-cell-receptor-signaling
#13
Sarah E Josefsson, Kanutte Huse, Arne Kolstad, Klaus Beiske, Daniela Pende, Chloé B Steen, Else Marit Inderberg, Ole Christian Lingjærde, Bjørn Østenstad, Erlend B Smeland, Ronald Levy, Jonathan M Irish, June H Myklebust
Purpose: T cells infiltrating follicular lymphoma (FL) tumors are considered dysfunctional, yet the optimal target for immune checkpoint blockade is unknown. Characterizing coinhibitory receptor expression patterns and signaling responses in FL T-cell subsets might reveal new therapeutic targets. Experimental Design: Surface expression of 9 coinhibitory receptors governing T-cell function was characterized in T-cell subsets from FL lymph node tumors and from healthy donor tonsils and peripheral blood samples, using high-dimensional flow cytometry...
February 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29202043/epstein-barr-virus-induces-adhesion-receptor-cd226-dnam-1-expression-during-primary-b-cell-transformation-into-lymphoblastoid-cell-lines
#14
Lisa Grossman, Chris Chang, Joanne Dai, Pavel A Nikitin, Dereje D Jima, Sandeep S Dave, Micah A Luftig
Epstein-Barr virus (EBV), an oncogenic herpesvirus, infects and transforms primary B cells into immortal lymphoblastoid cell lines (LCLs), providing a model for EBV-mediated tumorigenesis. EBV transformation stimulates robust homotypic aggregation, indicating that EBV induces molecules that mediate cell-cell adhesion. We report that EBV potently induced expression of the adhesion molecule CD226, which is not normally expressed on B cells. We found that early after infection of primary B cells, EBV promoted an increase in CD226 mRNA and protein expression...
November 2017: MSphere
https://www.readbyqxmd.com/read/29154208/characteristics-of-nk-cells-from-leukemic-microenvironment-in-mll-af9-induced-acute-myeloid-leukemia
#15
Feifei Yang, Rong Wang, Wenli Feng, Chong Chen, Xiao Yang, Lina Wang, Yuting Hu, Qian Ren, Guoguang Zheng
NK cells are indispensable components of tissue microenvironment and play vital in both innate and adaptive immunity. The activation and function of NK cells are affected by tumor microenvironments. NK cells are also important players in leukemic microenvironment. However, their characteristics in leukemic microenvironment, including maturation status, phenotype, subpopulations and functional roles especially immunoregulatory potential, have not been well established. Here, we studied these characteristics of NK cells in MLL-AF9 induced mouse acute myeloid leukemia (AML) model...
January 2018: Molecular Immunology
https://www.readbyqxmd.com/read/28920003/cd226-natural-killer-cells-fail-to-establish-stable-contacts-with-cancer-cells-and-show-impaired-control-of-tumor-metastasis-in-vivo
#16
Ji Sung Kim, Bo Ram Shin, Hong Kyung Lee, Jae Hee Lee, Ki Hun Kim, Jeong Eun Choi, A Young Ji, Jin Tae Hong, Youngsoo Kim, Sang-Bae Han
CD226 is an activating receptor expressed on natural killer (NK) cells, CD8(+) T cells, and other immune cells. Upon binding to its ligands expressed on target cells, CD226 activates intracellular signaling that triggers cytokine production and degranulation in NK cells. However, the role of CD226 in contact dynamics between NK and cancer cells has remained unclear. Our time-lapse images showed that individual wild-type CD226(+) NK cells contacted B16F10 melanoma cells for 23.7 min, but Cd226(-/-) NK cells only for 12...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28893624/cd8-t-cells-expressing-both-pd-1-and-tigit-but-not-cd226-are-dysfunctional-in-acute-myeloid-leukemia-aml-patients
#17
Mengjie Wang, Jin Bu, Maohua Zhou, Jessica Sido, Yu Lin, Guanfang Liu, Qiwen Lin, Xiuzhang Xu, Jianmei W Leavenworth, Erxia Shen
Acute myeloid leukemia (AML) is one of the most common types of leukemia among adults with an overall poor prognosis and very limited treatment management. Immune checkpoint blockade of PD-1 alone or combined with other immune checkpoint blockade has gained impressive results in murine AML models by improving anti-leukemia CD8+ T cell function, which has greatly promoted the strategy to utilize combined immune checkpoint inhibitors to treat AML patients. However, the expression profiles of these immune checkpoint receptors, such as co-inhibitory receptors PD-1 and TIGIT and co-stimulatory receptor CD226, in T cells from AML patients have not been clearly defined...
May 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28880014/chimeric-antigen-receptor-car-transduced-natural-killer-cells-in-tumor-immunotherapy
#18
REVIEW
Yuan Hu, Zhi-Gang Tian, Cai Zhang
Natural killer (NK) cells are potential effector cells in cell-based cancer immunotherapy, particularly in the control of hematological malignancies. The chimeric antigen receptor (CAR) is an artificially modified fusion protein that consists of an extracellular antigen recognition domain fused to an intracellular signaling domain. T cells genetically modified with a CAR have demonstrated remarkable success in the treatment of hematological cancers. Compared to T cells, CAR-transduced NK cells (CAR-NK) exhibit several advantages, such as safety in clinical use, the mechanisms by which they recognize cancer cells, and their abundance in clinical samples...
February 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28870470/poliovirus-receptor-more-than-a-simple-viral-receptor
#19
REVIEW
Jonathan R Bowers, James M Readler, Priyanka Sharma, Katherine J D A Excoffon
The human poliovirus receptor (PVR) is a cell surface protein with a multitude of functions in human biology. PVR was initially identified as the receptor for the human poliovirus and recent discoveries have given a greater insight into both its morphology and its function. Alternative splicing of the PVR gene results in a total of 4 alternatively spliced isoforms. Two of these isoforms lack a complete transmembrane domain and are considered soluble and block viral infection; the remaining two transmembrane isoforms differ only at their extreme C-terminal domains resulting in differential localization in epithelia and polarity of viral infection...
October 15, 2017: Virus Research
https://www.readbyqxmd.com/read/28702029/inflammation-related-gene-polymorphisms-associated-with-primary-immune-thrombocytopenia
#20
Ju Li, Sai Ma, Linlin Shao, Chunhong Ma, Chengjiang Gao, Xiao-Hui Zhang, Ming Hou, Jun Peng
Primary immune thrombocytopenia (ITP) is an acquired autoimmune disease characterized by a reduced platelet count and an increased risk of bleeding. Although immense research has improved our understanding of ITP, the pathogenesis remains unclear. Here, we investigated the involvement of 25 single-nucleotide polymorphisms (SNPs) of the inflammation-related genes, including CD24, CD226, FCRL3, IL2, IRF5, ITGAM, NLRP3, CARD8, PTPN22, SH2B2, STAT4, TNFAIP3, and TRAF1, in the pathogenesis and treatment response of ITP...
2017: Frontiers in Immunology
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