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https://www.readbyqxmd.com/read/28805812/t-bet-dependent-nkp46-innate-lymphoid-cells-regulate-the-onset-of-th17-induced-neuroinflammation
#1
Brandon Kwong, Rejane Rua, Yuanyuan Gao, John Flickinger, Yan Wang, Michael J Kruhlak, Jinfang Zhu, Eric Vivier, Dorian B McGavern, Vanja Lazarevic
The transcription factor T-bet has been associated with increased susceptibility to systemic and organ-specific autoimmunity, but the mechanism by which T-bet expression promotes neuroinflammation remains unknown. In this study, we demonstrate a cardinal role of T-bet-dependent NKp46(+) innate lymphoid cells (ILCs) in the initiation of CD4(+) TH17-mediated neuroinflammation. Loss of T-bet specifically in NKp46(+) ILCs profoundly impaired the ability of myelin-reactive TH17 cells to invade central nervous system (CNS) tissue and protected the mice from autoimmunity...
August 14, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28805342/deletion-of-the-activating-nk-cell-receptor-nkg2d-accelerates-rejection-of-cardiac-allografts
#2
Cornelia Fabritius, Paul Viktor Ritschl, Thomas Resch, Mario Roth, Susanne Ebner, Julia Günther, Vanessa Mellitzer, Anh-Vu Nguyen, Johann Pratschke, Martina Sauter, Karin Klingel, Katja Kotsch
It has already been shown that neutralization of the activating NK cell receptor NKG2D in combination with co-stimulation blockade prolongs graft survival of vascularized transplants. In order to clarify the underlying cellular mechanisms, we transplanted complete MHC-disparate BALB/c-derived cardiac grafts into C57BL/6 wildtypes or mice deficient for NKG2D (Klrk1(-/-) ). Although median survival was eight days for both recipient groups, we detected already at day 5 post-transplantation significantly greater intragraft frequencies of NKp46(+) NK cells in Klrk1(-/-) recipients than in wildtypes...
August 14, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28794456/activated-nk-cells-cause-placental-dysfunction-and-miscarriages-in-fetal-alloimmune-thrombocytopenia
#3
Issaka Yougbaré, Wei-She Tai, Darko Zdravic, Brigitta Elaine Oswald, Sean Lang, Guangheng Zhu, Howard Leong-Poi, Dawei Qu, Lisa Yu, Caroline Dunk, Jianhong Zhang, John G Sled, Stephen J Lye, Jelena Brkić, Chun Peng, Petter Höglund, B Anne Croy, S Lee Adamson, Xiao-Yan Wen, Duncan J Stewart, John Freedman, Heyu Ni
Miscarriage and intrauterine growth restriction (IUGR) are devastating complications in fetal/neonatal alloimmune thrombocytopenia (FNAIT). We previously reported the mechanisms for bleeding diatheses, but it is unknown whether placental, decidual immune cells or other abnormalities at the maternal-fetal interface contribute to FNAIT. Here we show that maternal immune responses to fetal platelet antigens cause miscarriage and IUGR that are associated with vascular and immune pathologies in murine FNAIT models...
August 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28778069/zbtb1-controls-nkp46-ror-gamma-t-innate-lymphoid-cell-ilc3-development
#4
Ying Lu, Xianyu Zhang, Nicolas Bouladoux, Saransh Neel Kaul, Kangxin Jin, Derek Sant'Angelo, Yasmine Belkaid, Damian Kovalovsky
Innate lymphoid cells (ILCs) play a central role conferring protection at the mucosal frontier. In this study, we have identified a requirement of the transcription factor Zbtb1 for the development of RORγt+ ILCs (ILC3s). Zbtb1-deficient mice lacked NKp46+ ILC3 cells in the lamina propria of the small and large intestine. This requirement of Zbtb1 was cell intrinsic, as NKp46+ ILC3s were not generated from Zbtb1-deficient progenitors in bone marrow chimeras and Zbtb1-deficient RORγt+ CCR6-NKp46- ILC3s didn't generate NKp46+ ILC3s in co-cultures with OP9-DL1 stroma...
July 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28771871/predicting-nk-cell-subsets-using-gene-expression-levels-in-peripheral-blood-and-endometrial-biopsy-specimens
#5
Michael L Davies, Svetlana V Dambaeva, Dimantha Katukurundage, Miroslava Repak, Alice Gilman-Sachs, Joanne Kwak-Kim, Kenneth D Beaman
PROBLEM: In molecular analysis of tissue biopsy specimens, one crucial aspect is characterization of immune cell populations. This is especially important for evaluation of uterine receptivity by assessing levels of lymphocyte populations including CD56(bright) CD16- uterine NK cells and CD56(dim) CD16+ conventional NK cells. Our objective was to investigate whether measuring total RNA transcripts from a tissue specimen would accurately reflect immune cell levels and be a new technique to assess immune cell subsets...
August 3, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28767405/the-integrative-clinical-impact-of-tumor-infiltrating-t-lymphocytes-and-nk-cells-in-relation-to-b-lymphocyte-and-plasma-cell-density-in-esophageal-and-gastric-adenocarcinoma
#6
Maria C Svensson, Carl Fredrik Warfvinge, Richard Fristedt, Charlotta Hedner, David Borg, Jakob Eberhard, Patrick Micke, Björn Nodin, Karin Leandersson, Karin Jirström
BACKGROUND: Several studies have demonstrated a prognostic impact of tumor-infiltrating T lymphocytes and natural killer (NK) cells in esophageal and gastric adenocarcinoma, but whether these associations differ by the density of tumor-infiltrating immune cells of the B cell lineage remains largely unknown. RESULTS: High infiltration of any T and NK lymphocytes investigated was in general associated with a favorable prognosis, but the strongest beneficial prognostic impact was seen in combination with high B lymphocyte infiltration...
July 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28747319/frontline-science-a-hyporesponsive-subset-of-rat-nk-cells-negative-for-ly49s3-and-nkr-p1b-are-precursors-to-the-functionally-mature-nkr-p1b-subset
#7
Amanda Sudworth, John T Vaage, Marit Inngjerdingen, Lise Kveberg
Rat NK cells are divided into major subsets expressing either Ly49 receptors or the inhibitory NKR-P1B receptor in conjunction with NKG2A/C/E receptors. A minor subset of NKp46(+) cells lacking expression of both Ly49 receptors and NKR-P1B is present in blood and spleen and is associated with decreased functional competence. We hypothesized that this subset may represent precursors to Ly49(+) and/or NKR-P1B(+) NK cells. When cultured in vitro in IL-2 and IL-15 or adoptively transferred to syngeneic hosts, a portion of NKR-P1B (-) Ly49s3 (-) cells transformed to express NKR-P1B, but very little Ly49s3...
July 26, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28724773/nkp46-recognizes-the-sigma1-protein-of-reovirus-implications-for-reovirus-based-cancer-therapy
#8
Yotam Bar-On, Yoav Charpak-Amikam, Ariella Glasner, Batya Isaacson, Alexandra Duev-Cohen, Pinchas Tsukerman, Alexander Varvak, Michal Mandelboim, Ofer Mandelboim
The recent approval of onclolytic virus for therapy of melanoma patients has increased the need for precise evaluation of the mechanisms by which oncolytic viruses affect tumor growth. Here we show that the human NK activating receptor, NKp46, and its mouse orthologous protein, NCR1, recognize the reovirus sigma1 protein in a sialic-acid-dependent manner. We identify NKp46/NCR1 binding sites to sigma1 and show that sigma1 binding by NKp46/NCR1 leads to NK cell activation in vitro Finally, we demonstrate that NCR1 activation is essential for reovirus-based therapy in vivo Collectively, we identified sigma1 as a novel ligand for NKp46/NCR1 and demonstrated that NKp46/NCR1 is needed for both clearance of reovirus infections and reovirus-based tumor therapy...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28720115/expression-pattern-of-cd11c-on-lung-immune-cells-after-disseminated-murine-cytomegalovirus-infection
#9
Yi Liao, Xinglou Liu, Yuan Huang, Heyu Huang, Yuanyuan Lu, Yanan Zhang, Sainan Shu, Feng Fang
BACKGROUND: Cytomegalovirus (CMV) infection occurs frequently and is widespread globally. Numerous studies have shown that various types of immune cells play roles in mediating the response to CMV infection. CD11c, a commonly used dendritic cell (DC) marker, is expressed by other immune cells as well, such as T cells. This study analyzed the immune cells that express CD11c and monitored the expression level of their specific cell surface markers in the lung following a disseminated murine (M)CMV infection...
July 18, 2017: Virology Journal
https://www.readbyqxmd.com/read/28694168/characterizing-porcine-invariant-natural-killer-t-cells-a-comparative-study-with-nk-cells-and-t-cells
#10
Guan Yang, Bianca L Artiaga, Sarah T Lewis, John P Driver
CD1d-restricted invariant natural killer T (iNKT) cells are innate-like T cells that share phenotypic characteristics of both NK and conventional T cells (Tconv). Although iNKT cells have been well characterized in mice and humans, functional CD1d and CD1d-restricted iNKT cells are not universally expressed in mammals. Swine express iNKT cells that can be detected using α-galactosylceramide (α-GalCer)-loaded CD1d tetramers. In the present study, we characterized iNKT cells from the blood, spleen, lymph node, lung and liver of commercial mixed-breed pigs, and compared their phenotype to NK cells and Tconv...
July 8, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28643847/ncr1-deficiency-diminishes-the-generation-of-protective-murine-cytomegalovirus-antibodies-by-limiting-follicular-helper-t-cell-maturation
#11
Antonija Miletic, Maja Lenartic, Branka Popovic, Ilija Brizic, Tihana Trsan, Karmela Miklic, Ofer Mandelboim, Astrid Krmpotic, Stipan Jonjic
NKp46/NCR1 is an activating NK-cell receptor implicated in the control of various viral and bacterial infections. Recent findings also suggest that it plays a role in shaping the adaptive immune response to pathogens. Using NCR1-deficient (NCR1(gfp/gfp) ) mice we provide evidence for the role of NCR1 in antibody response to mouse cytomegalovirus infection (MCMV). The absence of NCR1 resulted in impaired maturation, function and NK-cell migration to regional lymph nodes. In addition, CD4(+) T-cell activation and follicular helper T-cell (Tfh) generation were reduced, leading to inferior germinal center (GC) B-cell maturation...
June 23, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28641645/-subtype-and-functional-biomarker-changes-of-nk-cells-in-peripheral-blood-of-patients-with-myelodysplastic-syndrome
#12
Shu-Juan Xu, Zong-Hong Shao, Rong Fu, Hua-Quan Wang, Hui Liu, Chun-Yan Liu, Wei Zhang
OBJECTIVE: To analyze the subtype and functional biomarker expression changes of natural kill cells(NK) in peripheral blood of patients with myelodysplastic syndrome(MDS) and normal people, so as to evaluate the relationships between these changes and hematopoietic functions and to explore the role of NK cells in the pathogenesis of MDS. METHODS: The quantity of NK cells and the expression of biomarkers(NKp30,NKp46,NKG2A) on NK cells were detected by flow cytometry in 35 MDS patients from 2015 to 2016 in our hospital and 34 normal controls...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28639033/functional-restoration-of-cd56-bright-nk-cells-facilitates-immune-control-via-il-15-and-nkg2d-in-patients-under-antiviral-treatment-for-chronic-hepatitis-b
#13
Tao Chen, Lin Zhu, Aichao Shi, Lin Ding, Xiaoping Zhang, Zhenmin Tan, Wei Guo, Weiming Yan, Meifang Han, Jidong Jia, Xiaoping Luo, Detlef Schuppan, Qin Ning
BACKGROUND AND AIMS: Hepatitis B virus (HBV) is intrinsically immunogenic, with long-lasting immune control in many patients. However, the mechanisms and key cell types underlying effective immune control are incompletely understood. METHODS: We studied the restoration of natural killer (NK) cell numbers and function post antiviral treatment in 52 hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients who received telbivudine (LdT) for 48 weeks...
June 20, 2017: Hepatology International
https://www.readbyqxmd.com/read/28638068/microbiota-derived-butyrate-suppresses-group-3-innate-lymphoid-cells-in-terminal-ileal-peyer-s-patches
#14
Sae-Hae Kim, Byeol-Hee Cho, Hiroshi Kiyono, Yong-Suk Jang
The regional specialization of intestinal immune cells is affected by the longitudinal heterogeneity of environmental factors. Although the distribution of group 3 innate lymphoid cells (ILC3s) is well characterized in the lamina propria, it is poorly defined in Peyer's patches (PPs) along the intestine. Given that PP ILC3s are closely associated with mucosal immune regulation, it is important to characterize the regulatory mechanism of ILC3s. Here, we found that terminal ileal PPs of specific pathogen-free (SPF) mice have fewer NKp46(+) ILC3s than jejunal PPs, while there was no difference in NKp46(+) ILC3 numbers between terminal ileal and jejunal PPs in antibiotics (ABX)-treated mice...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28633489/effects-of-early-pregnancy-on-uterine-lymphocytes-and-endometrial-expression-of-immune-regulatory-molecules-in-dairy-heifers1
#15
Sreelakshmi Vasudevan, Manasi M Kamat, Sadhat S Walusimbi, Joy L Pate, Troy L Ott
Natural killer (NK) cells are essential for establishment of human and rodent pregnancies. The function of these and other cytotoxic T cells (CTL) is controlled by stimulatory and inhibitory signaling. A role for cytotoxic cells during early pregnancy in cattle has not been described, but regulation of their function at the fetal-maternal interface is thought to be critical for conceptus survival. The hypothesis that the relative abundance of CTL and expression of inhibitory signaling molecules is increased by the conceptus during early pregnancy was tested...
June 19, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28614370/the-hemagglutinin-neuramidinase-protein-of-newcastle-disease-virus-upregulates-expression-of-the-trail-gene-in-murine-natural-killer-cells-through-the-activation-of-syk-and-nf-%C3%AE%C2%BAb
#16
Ying Liang, De-Zhi Song, Shuang Liang, Zeng-Feng Zhang, Ling-Xi Gao, Xiao-Hui Fan
Newcastle disease virus (NDV) is responsible for tumoricidal activity in vitro and in vivo. However, the mechanisms that lead to this activity are unclear. Natural killer cells are able to induce apoptosis of tumor cells through multiple pathways, including the tumor necrosis factor-related apoptosis-inducing ligand-death receptor pathway. We previously showed that exposure of NK and T cells to NDV resulted in enhanced tumoricidal activity that was mediated by upregulated expression of the TRAIL gene, via an interferon gamma -dependent pathway...
2017: PloS One
https://www.readbyqxmd.com/read/28603523/kir3ds1-mediated-recognition-of-hla-b51-modulation-of-kir3ds1-responsiveness-by-self-hla-b-allotypes-and-effect-on-nk-cell-licensing
#17
Simona Carlomagno, Michela Falco, Maria Bono, Claudia Alicata, Lucia Garbarino, Michela Mazzocco, Lorenzo Moretta, Alessandro Moretta, Simona Sivori
Several studies described an association between killer-cell immunoglobulin-like receptor (KIR)/HLA gene combinations and clinical outcomes in various diseases. In particular, an important combined role for KIR3DS1 and HLA-B Bw4-I80 in controlling viral infections and a higher protection against leukemic relapses in donor equipped with activating KIRs in haplo-HSCT has been described. Here, we show that KIR3DS1 mediates positive signals upon recognition of HLA-B*51 (Bw4-I80) surface molecules on target cells and that this activation occurs only in Bw4-I80(neg) individuals, including those carrying particular KIR/HLA combination settings...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28589939/wash-maintains-nkp46-ilc3-cells-by-promoting-ahr-expression
#18
Pengyan Xia, Jing Liu, Shuo Wang, Buqing Ye, Ying Du, Zhen Xiong, Ze-Guang Han, Liang Tong, Zusen Fan
Innate lymphoid cells (ILCs) communicate with other haematopoietic and non-haematopoietic cells to regulate immunity, inflammation and tissue homeostasis. How these ILC lineages develop and are maintained is not clear. Here we show that WASH is highly expressed in the nucleus of group 3 ILCs (ILC3s). WASH deletion impairs the cell pool of NKp46(+) ILC3s. In NKp46(+) ILC3s, WASH recruits Arid1a to the Ahr promoter thus activating AHR expression. WASH deletion in ILC3s decreases the number of NKp46(+) ILC3s. Moreover, Arid1a deletion impedes AHR expression and impairs the maintenance of NKp46(+) ILC3s...
June 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/28581441/nk-cell-heparanase-controls-tumor-invasion-and-immune-surveillance
#19
Eva M Putz, Alyce J Mayfosh, Kevin Kos, Deborah S Barkauskas, Kyohei Nakamura, Liam Town, Katharine J Goodall, Dean Y Yee, Ivan Kh Poon, Nikola Baschuk, Fernando Souza-Fonseca-Guimaraes, Mark D Hulett, Mark J Smyth
NK cells are highly efficient at preventing cancer metastasis but are infrequently found in the core of primary tumors. Here, have we demonstrated that freshly isolated mouse and human NK cells express low levels of the endo-β-D-glucuronidase heparanase that increase upon NK cell activation. Heparanase deficiency did not affect development, differentiation, or tissue localization of NK cells under steady-state conditions. However, mice lacking heparanase specifically in NK cells (Hpsefl/fl NKp46-iCre mice) were highly tumor prone when challenged with the carcinogen methylcholanthrene (MCA)...
June 30, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28558022/different-features-of-v%C3%AE-2-t-and-nk-cells-in-fatal-and-non-fatal-human-ebola-infections
#20
Eleonora Cimini, Domenico Viola, Mar Cabeza-Cabrerizo, Antonella Romanelli, Nicola Tumino, Alessandra Sacchi, Veronica Bordoni, Rita Casetti, Federica Turchi, Federico Martini, Joseph A Bore, Fara Raymond Koundouno, Sophie Duraffour, Janine Michel, Tobias Holm, Elsa Gayle Zekeng, Lauren Cowley, Isabel Garcia Dorival, Juliane Doerrbecker, Nicole Hetzelt, Jonathan H J Baum, Jasmine Portmann, Roman Wölfel, Martin Gabriel, Osvaldo Miranda, Graciliano Díaz, José E Díaz, Yoel A Fleites, Carlos A Piñeiro, Carlos M Castro, Lamine Koivogui, N'Faly Magassouba, Boubacar Diallo, Paula Ruibal, Lisa Oestereich, David M Wozniak, Anja Lüdtke, Beate Becker-Ziaja, Maria R Capobianchi, Giuseppe Ippolito, Miles W Carroll, Stephan Günther, Antonino Di Caro, César Muñoz-Fontela, Chiara Agrati
BACKGROUND: Human Ebola infection is characterized by a paralysis of the immune system. A signature of αβ T cells in fatal Ebola infection has been recently proposed, while the involvement of innate immune cells in the protection/pathogenesis of Ebola infection is unknown. Aim of this study was to analyze γδ T and NK cells in patients from the Ebola outbreak of 2014-2015 occurred in West Africa, and to assess their association with the clinical outcome. METHODOLOGY/PRINCIPAL FINDINGS: Nineteen Ebola-infected patients were enrolled at the time of admission to the Ebola Treatment Centre in Guinea...
May 2017: PLoS Neglected Tropical Diseases
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