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Olivier Lucar, Mariama Sadjo Diallo, Charles Bayard, Assia Samri, Nadine Tarantino, Patrice Debré, Rodolphe Thiébaut, Françoise Brun-Vézinet, Sophie Matheron, Rémi Cheynier, Vincent Vieillard
OBJECTIVE: HIV-1 and HIV-2 differ notably in their epidemiology, with worldwide HIV-1 spread and HIV-2 mainly confined to West Africa. Natural killer (NK) cells are critical antiviral effectors of the immune system; however, limited information is available about these innate effector cells during HIV-2 infection. METHOD: In this study, 24 untreated HIV-2-infected patients were analyzed and compared with 21 long-term nonprogressor and 10 controller HIV-1 patients, and healthy donors...
October 15, 2018: AIDS
Martina Bonacini, Alessandra Soriano, Alessandro Zerbini, Eleonora Calò, Luca Cimino, Francesco Muratore, Luigi Fontana, Luca Braglia, Maria Parmeggiani, Carlo Salvarani, Stefania Croci
Behçet disease (BD) is an inflammatory systemic disease with a fluctuating course, which can affect the skin, eyes, central nervous system, musculoskeletal, gastrointestinal, and vascular systems. No laboratory tests are currently available for the diagnosis of BD and monitoring disease activity. Moreover there is a lack of knowledge on BD pathogenesis. This study focused on circulating Natural Killer (NK), NKT and T cells evaluated as CD3neg CD56pos , CD3pos CD56pos , and CD3pos CD56neg . Peripheral blood mononuclear cells (PBMCs) were collected from 38 BD patients and 20 healthy controls (HC)...
2018: Frontiers in Immunology
Hiroki Kabata, Kazuyo Moro, Shigeo Koyasu
Group 2 innate lymphoid cells (ILC2s) play critical roles in the induction of type 2 inflammation, response to parasite infection, metabolic homeostasis, and tissue repair. These multifunctional roles of ILC2s are tightly controlled by complex regulatory systems in the local microenvironment, the disruption of which may cause various health problems. This review summarizes up-to-date knowledge regarding positive and negative regulators for ILC2s based on their function and signaling pathways, including activating cytokines (IL-33, IL-25; MAPK, NF-κB pathways), co-stimulatory cytokines (IL-2, IL-7, IL-9, TSLP; STAT5, IL-4; STAT6, TNF superfamily; MAPK, NF-κB pathways), suppressive cytokines (type1 IFNs, IFN-γ, IL-27; STAT1, IL-10, TGF-β), transdifferentiation cytokines (IL-12; STAT4, IL-1β, IL-18), lipid mediators (LTC4, LTD4, LTE4, PGD2; Ca2+ -NFAT pathways, PGE2, PGI2; AC/cAMP/PKA pathways, LXA4, LTB4), neuropeptides (NMU; Ca2+ -NFAT, MAPK pathways, VIP, CGRP, catecholamine, acetylcholine), sex hormones (androgen, estrogen), nutrients (butyrate; HDAC inhibitors, vitamins), and cell-to-cell interactions (ICOSL-ICOS; STAT5, B7-H6-NKp30, E-cadherin-KLRG1)...
November 2018: Immunological Reviews
Bin Han, Fang-Yuan Mao, Yong-Liang Zhao, Yi-Pin Lv, Yong-Sheng Teng, Mubing Duan, Weisan Chen, Ping Cheng, Ting-Ting Wang, Zhong-Yuan Liang, Jin-Yu Zhang, Yu-Gang Liu, Gang Guo, Quan-Ming Zou, Yuan Zhuang, Liu-Sheng Peng
Natural killer (NK) cell activity is influenced by a complex integration of signaling pathways activated downstream of both activating and inhibitory surface receptors. The tumor microenvironment can suppress NK cell activity, and there is a great clinical interest in understanding whether modulating tumor-mediated NK cell suppression and/or boosting preexisting NK cell numbers in cancer patients is therapeutically viable. To this light, we characterized the surface receptor phenotypes of peripheral blood NK cells and examined their clinical relevance to human gastric cancer (GC)...
2018: Journal of Immunology Research
Gemma A Foulds, Jayakumar Vadakekolathu, Tarek M A Abdel-Fatah, Divya Nagarajan, Stephen Reeder, Catherine Johnson, Simon Hood, Paul M Moseley, Stephen Y T Chan, A Graham Pockley, Sergio Rutella, Stephanie E B McArdle
Background: Interactions between the immune system and tumors are highly reciprocal in nature, leading to speculation that tumor recurrence or therapeutic resistance could be influenced or predicted by immune events that manifest locally, but can be detected systemically. Methods: Multi-parameter flow cytometry was used to examine the percentage and phenotype of natural killer (NK) cells, myeloid-derived suppressor cells (MDSCs), monocyte subsets and regulatory T (Treg) cells in the peripheral blood of of 85 patients with breast cancer (50 of whom were assessed before and after one cycle of anthracycline-based chemotherapy), and 23 controls...
2018: Frontiers in Immunology
Fumihiro Hirata, Kohei Ishiyama, Yuka Tanaka, Tsuyoshi Kobayashi, Masakazu Hashimoto, Yoshihiro Saeki, Nobuki Ishida, Kazuhiro Taguchi, Junko Tanaka, Koji Arihiro, Hideki Ohdan
Aim: We investigated the chemotherapy effect of resectable colorectal cancer with liver metastasis (CRLM) on the function of intrahepatic immune cells. Methods: We classified patients into adjuvant chemotherapy (bevacizumab+CapeOX) after hepatectomy group (group A) and neoadjuvant chemotherapy followed by hepatectomy group (group B), and collected peripheral blood mononuclear cells (PBMC) and liver mononuclear cells (LMNC) to ascertain phenotypic and functional differences...
September 2018: Annals of gastroenterological surgery
Kenichiro Ito, Ryo Shiraishi, Koji Higai
Natural killer (NK) cells play an important role in tumor immunity and infection control. The natural cytotoxicity receptors (NCRs) NKp46, NKp44 and NKp30 are involved in the control of the activation of NK cells. Few reports have investigated the ligands of NCRs. We previously reported the NCRs binding affinity to heparin and glycosaminoglycans. We also showed that multimeric sialyl Lewis X-expressing transferrin, secreted by human hepatoma HepG2 cells, binds to NKp46 and NKp44, but not to NKp30. In this study, we investigated the binding between NCRs and glycolipids...
2018: Biological & Pharmaceutical Bulletin
Yiting Li, Yingfu Zeng, Guofen Zeng, Jianguo Li, Xiaohong Zhang, Qingxian Cai, Youming Chen, Chao-Shuang Lin
Currently, hepatitis C antiviral therapy is entering a new era with the use of direct-acting antiviral (DAA) agents. However, the precise immunological influences of DAA therapy in patients with chronic hepatitis C (CHC) are insufficiently understood. This study aimed to investigate the effects of DAA therapy on the frequency of myeloid-derived suppressor cells (MDSCs), T lymphocytes, and natural killer (NK) cells in patients with CHC. Thirty-two treatment-naive CHC patients were treated with DAA therapy, and the frequency of immune cells was analyzed by flow cytometry at various time points during and after therapy...
September 1, 2018: Journal of Medical Virology
Stefania Mantovani, Barbara Oliviero, Andrea Lombardi, Stefania Varchetta, Dalila Mele, Angelo Sangiovanni, Giorgio Rossi, Matteo Donadon, Guido Torzilli, Cristiana Soldani, Camillo Porta, Paolo Pedrazzoli, Silvia Chiellino, Roberto Santambrogio, Enrico Opocher, Marcello Maestri, Stefano Bernuzzi, Armando Rossello, Sophie Clément, Claudio De Vito, Laura Rubbia-Brandt, Francesco Negro, Mario U Mondelli
The activating natural cytotoxicity receptor NKp30 is critical for natural killer (NK) cell function and tumor immune surveillance. The natural cytotoxicity receptor-3 (NCR3) gene is transcribed into several splice variants whose physiological relevance is still incompletely understood. In this study, we investigated the role of NKp30 and its major ligand B7 homolog 6 (B7-H6) in patients with hepatocellular carcinoma (HCC). Peripheral blood NK cell phenotype was skewed toward a defective/exhausted immune profile with decreased frequencies of cells expressing NKp30 and natural killer group 2 member d (NKG2D) and an increased proportion of cells expressing T-cell immunoglobulin and mucin-domain containing-3 (Tim-3)...
August 28, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Arum Park, Yunhee Lee, Mi Sun Kim, Young Ju Kang, Young-Jun Park, Haiyoung Jung, Tae-Don Kim, Hee Gu Lee, Inpyo Choi, Suk Ran Yoon
Natural killer (NK) cells play important roles in immune surveillance. However, the tumor microenvironment suppresses NK cell function and allows cancer cells to evade immune detection. In this study, we investigated whether the thyroid cancer cell microenvironment has this effect on NK cells. We found that prostaglandin (PG) E2 produced by thyroid cancer cells suppressed the cytolytic activity of NK cells by inhibiting the expression of the natural cytotoxicity receptors NKp44 and NKp30 and the death receptor tumor necrosis factor-related apoptosis-inducing ligand...
2018: Frontiers in Immunology
Katherine Walwyn-Brown, Karolin Guldevall, Mezida Saeed, Daniela Pende, Björn Önfelt, Andrew S MacDonald, Daniel M Davis
Cross-talk between NK cells and dendritic cells (DCs) is important in Th1 immune responses, including antitumor immunity and responses to infections. DCs also play a crucial role in polarizing Th2 immunity, but the impact of NK cell-DC interactions in this context remains unknown. In this study, we stimulated human monocyte-derived DCs in vitro with different pathogen-associated molecules: LPS or polyinosinic-polycytidylic acid, which polarize a Th1 response, or soluble egg Ag from the helminth worm Schistosoma mansoni , a potent Th2-inducing Ag...
October 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Ruben C Hoogeveen, Georg M Lauer
Kim and colleagues studied a large cohort of adults with acute symptomatic HAV infection. They found pervasive and profound CD8 T cell activation in the blood of these patients, together with increased T cell proliferation and expression of cytotoxic molecules in a substantial proportion and often the majority of circulating CD8 T cells. The degree of overall activation, proliferation and cytotoxic capacity was tightly correlated with liver damage, as measured by ALT serum levels. Critically, they showed that this activated CD8 T cell phenotype was not limited to HAV-specific T cells but was found on multiple HAV-unrelated specificities they tested, i...
August 13, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Josephine A Drury, Kirstin L Parkin, Lucy Coyne, Emma Giuliani, Asgerally T Fazleabas, Dharani K Hapangama
BACKGROUND: Endometriosis is a common condition associated with growth of endometrial-like tissue beyond the uterine cavity. Previous reports have suggested a role for uNK cells in the pathogenesis of endometriosis postulating that survival and accumulation of menstrual endometrial tissue in the peritoneal cavity may relate to a reduction in the cytotoxic activity of peripheral blood NK cells. We aimed to assess the differences in percentage of uNK cells and their phenotypical characterization in eutopic and ectopic endometrial samples from women with and without endometriosis and baboons with induced endometriosis...
July 18, 2018: Reproductive Biology and Endocrinology: RB&E
Avishay Edri, Avishai Shemesh, Muhammed Iraqi, Omri Matalon, Michael Brusilovsky, Uzi Hadad, Olga Radinsky, Orly Gershoni-Yahalom, John M Dye, Ofer Mandelboim, Mira Barda-Saad, Leslie Lobel, Angel Porgador
The Ebola virus (EBOV) uses evasion mechanisms that directly interfere with host T-cell antiviral responses. By steric shielding of human leukocyte antigen class-1, the Ebola glycoprotein (GP) blocks interaction with T-cell receptors (TCRs), thus rendering T cells unable to attack virus-infected cells. It is likely that this mechanism could promote increased natural killer (NK) cell activity against GP-expressing cells by preventing the engagement of NK inhibitory receptors; however, we found that primary human NK cells were less reactive to GP-expressing HEK293T cells...
2018: Frontiers in Immunology
Margareta P Correia, Ana Stojanovic, Katharina Bauer, Dilafruz Juraeva, Lars-Oliver Tykocinski, Hanns-Martin Lorenz, Benedikt Brors, Adelheid Cerwenka
CD8+ T cells are considered prototypical cells of adaptive immunity. Here, we uncovered a distinct CD8+ T cell population expressing the activating natural killer (NK) receptor NKp30 in the peripheral blood of healthy individuals. We revealed that IL-15 could de novo induce NKp30 expression in a population of CD8+ T cells and drive their differentiation toward a broad innate transcriptional landscape. The adaptor FcεRIγ was concomitantly induced and was shown to be crucial to enable NKp30 cell-surface expression and function in CD8+ T cells...
June 26, 2018: Proceedings of the National Academy of Sciences of the United States of America
A Shi, X Zhang, F Xiao, L Zhu, W Yan, M Han, X Luo, T Chen, Q Ning
HBV surface antigen (HBsAg) reduction is well observed in chronic hepatitis B (CHB) patients treated with pegylated interferon alpha-2a (PegIFNα). However, the mechanism of HBsAg suppression has not been fully elucidated. Twenty-seven of 55 entecavir-treated CHB e antigen positive patients were switched to PegIFNα treatment (Group A) whereas 28 patients continued entecavir treatment (Group B). The percentage or absolute number of CD56bright /CD56dim NK cells, expression of receptors and cytokines were evaluated by flow cytometry for 48 weeks and correlated with treatment efficacy...
June 11, 2018: Journal of Viral Hepatitis
Aude Le Roy, Thomas Prébet, Rémy Castellano, Armelle Goubard, Florence Riccardi, Cyril Fauriat, Samuel Granjeaud, Audrey Benyamine, Céline Castanier, Florence Orlanducci, Amira Ben Amara, Frédéric Pont, Jean-Jacques Fournié, Yves Collette, Jean-Louis Mege, Norbert Vey, Daniel Olive
Immunomodulatory drugs (IMiDs) are anticancer drugs with immunomodulatory, anti-angiogenesis, anti-proliferative, and pro-apoptotic properties. IMiDs are currently used for the treatment of multiple myeloma, myelodysplastic syndrome, and B-cell lymphoma; however, little is known about efficacy in acute myeloid leukemia (AML). We proposed in this study to investigate the relevance of IMiDs therapy for AML treatment. We evaluated the effect of IMiDs on primary AML blasts ( n  = 24), and the impact in natural killer (NK) cell-mediated immunosurveillance of AML...
2018: Frontiers in Immunology
Catherine S Forconi, Cormac P Cosgrove, Pryia Saikumar-Lakshmi, Christina E Nixon, Joslyn Foley, John Michael Ong'echa, Juliana A Otieno, Galit Alter, Christian Münz, Ann M Moormann
Natural killer (NK) cells are critical for restricting viral infections and mediating tumor immunosurveillance. Epstein-Barr virus (EBV) and Plasmodium falciparum malaria are known risk factors for endemic Burkitt lymphoma (eBL), the most common childhood cancer in equatorial Africa. To date, the composition and function of NK cells have not been evaluated in eBL etiology or pathogenesis. Therefore, using multiparameter flow cytometry and in vitro killing assays, we compared NK cells from healthy children and children diagnosed with eBL in Kenya...
May 22, 2018: Blood Advances
Soo-Hyeon Lee, Dong-Jun Shin, Yoseop Kim, Cheol-Jung Kim, Je-Jung Lee, Mee Sun Yoon, Tung Nguyen Thanh Uong, Dohyeon Yu, Ji-Youn Jung, Duck Cho, Bock-Gie Jung, Sang-Ki Kim, Guk-Hyun Suh
Natural killer (NK) cells play a pivotal role in the immune response against infections and malignant transformation, and adopted transfer of NK cells is thought to be a promising therapeutic approach for cancer patients. Previous reports describing the phenotypic features of canine NK cells have produced inconsistent results. Canine NK cells are still defined as non-B and non-T (CD3- CD21- ) large granular lymphocytes. However, a few reports have demonstrated that canine NK cells share the phenotypic characteristics of T lymphocytes, and that CD3+ CD5dim CD21- lymphocytes are putative canine NK cells...
2018: Frontiers in Immunology
Leticía Huergo-Zapico, Monica Parodi, Claudia Cantoni, Chiara Lavarello, Juan L Fernández-Martínez, Andrea Petretto, Enrique J DeAndrés-Galiana, Mirna Balsamo, Alejandro López-Soto, Gabriella Pietra, Mattia Bugatti, Enrico Munari, Marcella Marconi, Maria Cristina Mingari, William Vermi, Lorenzo Moretta, Segundo González, Massimo Vitale
Tumor cell plasticity is a major obstacle for the cure of malignancies as it makes tumor cells highly adaptable to microenvironmental changes, enables their phenotype switching among different forms, and favors the generation of prometastatic tumor cell subsets. Phenotype switching toward more aggressive forms involves different functional, phenotypic, and morphologic changes, which are often related to the process known as epithelial-mesenchymal transition (EMT). In this study, we report natural killer (NK) cells may increase the malignancy of melanoma cells by inducing changes relevant to EMT and, more broadly, to phenotype switching from proliferative to invasive forms...
July 15, 2018: Cancer Research
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