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Vivien Béziat, Hugo Hilton, Paul J Norman, James A Traherne
Killer-cell immunoglobulin-like receptors (KIRs) are components of two fundamental biological systems essential for human health and survival. Firstly, they contribute to host immune response, both innate and adaptive, through their expression by natural killer (NK) cells and T cells. Secondly, KIR play a key role in regulating placentation, and hence reproductive success. Analogous to the diversity of their HLA class I ligands, KIR are extremely polymorphic. In this review, we describe recent developments, fuelled by methodological advances, which are helping to decipher the KIR system in terms of haplotypes, polymorphisms, expression patterns and their ligand interactions...
October 25, 2016: Immunology
Rajarsi Mandal, Yasin Şenbabaoğlu, Alexis Desrichard, Jonathan J Havel, Martin G Dalin, Nadeem Riaz, Ken-Wing Lee, Ian Ganly, A Ari Hakimi, Timothy A Chan, Luc G T Morris
Recent clinical trials have demonstrated a clear survival advantage in advanced head and neck squamous cell carcinoma (HNSCC) patients treated with immune checkpoint blockade. These emerging results reveal that HNSCC is one of the most promising frontiers for immunotherapy research. However, further progress in head and neck immuno-oncology will require a detailed understanding of the immune infiltrative landscape found in these tumors. We leveraged transcriptome data from 280 tumors profiled by The Cancer Genome Atlas (TCGA) to comprehensively characterize the immune landscape of HNSCC in order to develop a rationale for immunotherapeutic strategies in HNSCC and guide clinical investigation...
October 20, 2016: JCI Insight
Silvia Pesce, Lorenzo Moretta, Alessandro Moretta, Emanuela Marcenaro
Innate and adaptive immunity has evolved complex molecular mechanisms regulating immune cell migration to facilitate the dynamic cellular interactions required for its function involving the chemokines and their receptors. One important chemokine receptor in the immune system is represented by CCR7. Together with its ligands CCL19 and CCL21, this chemokine receptor controls different arrays of migratory events, both in innate and adaptive immunity, including homing of CD56(bright) NK cells, T cells, and DCs to lymphoid compartments, where T cell priming occurs...
2016: Frontiers in Immunology
G Kamkamidze, M Butsashvili, K Gendzekhadze
Hepatitis C virus (HCV) infection remains one of the most important blood-borne diseases worldwide with about 130-170 million people chronically infected with hepatitis C virus, and more than 350 000 people die from hepatitis C-related liver diseases each year. Infection with HCV becomes chronic in approximately 80% of cases, while in up to 20% of cases hepatitis C virus is cleared from the human organism. Chronic infections of hepatitis C often leads to the end-stage liver diseases such as cirrhosis and hepatocellular carcinoma...
September 2016: Georgian Medical News
Qi-Lei Chen, Lin Zhu, Yi-Na Tang, Hiu-Yee Kwan, Zhong-Zhen Zhao, Hu-Biao Chen, Tao Yi
Herbal healthcare products are used worldwide as relatively safe and effective alternatives to allopathic drugs. Saussurea laniceps Hand.-Mazz.(SL), S. medusa Maxim. (SM) and S. involucrata (Kar. et Kir.) Sch.Bip. (SI) are three sources of the renowned "snow lotus" Chinese Materia Medica for treating inflammatory diseases. The three species have different therapeutic effects, among which SL has been proved to be the most potent, but they are frequently confused on the market and in the academic community. An ultra-high performance liquid chromatography-diode array detector-quadrupole time of flight-mass spectrometry (UPLC-DAD-QTOF-MS) method was developed and used to analyze 49 herbal samples for species analysis and overall quality evaluation...
October 20, 2016: Drug Testing and Analysis
Kate Stringaris, David Marin, A John Barrett, Robert Hills, Catherine Sobieski, Kai Cao, Jerome G Saltarrelli, May Daher, Hila Shaim, Nathaniel Smith, David Linch, Rosemary Gale, Christopher Allen, Takuya Sekine, Rohtesh Mehta, Richard Champlin, Elizabeth J Shpall, Hagop Kantarjian, Guillermo Garcia-Manero, Katayoun Rezvani
Myelodysplastic syndromes (MDS) are a group of hematopoietic disorders affecting the myeloid lineage, characterized by cytopenias and clonal evolution to acute myeloid leukemia (AML). We hypothesized that natural killer (NK) cells and their activating killer immunoglobulin-like receptors (aKIRs) influence the immune surveillance and clinical outcome of patients with MDS. Here, we first examined the distribution of aKIR genes and haplotype in two independent cohorts of MDS and AML patients. The median number of aKIR genes was lower in MDS patients than healthy controls (2 vs...
October 19, 2016: Blood
Shixiao Zhang, Zan Guo, Shijie Yang, Huijuan Ma, Congrui Fu, Sheng Wang, Yi Zhang, Yixian Liu, Jie Hu
OBJECTIVE: Providing adequate protection against cerebral ischemia remains an unrealized goal. The present study was aimed at testing whether chronic intermittent hypobaric hypoxia (CIHH) would have protective effects against cerebral ischemia and investigating the potential role of mitochondrial membrane ATP-sensitive potassium channel (mitoKATP) in this effect. METHODS: Ischemia was induced in rats by occlusion of bilateral common carotid arteries for 8min on day 2 after bilateral vertebral arteries were permanently electrocauterized and CIHH was simulated in a hypoxic chamber...
October 16, 2016: Neuroscience Letters
Ashley Moffett, Olympe Chazara, Francesco Colucci, Martin H Johnson
A distinctive type of (uterine) natural killer (NK) cell is present in the uterine decidua during the period of placental formation. Uterine NK cells express members of the killer immunoglobulin-like receptor (KIR) family that bind to parental HLA-C molecules on the invading placental trophoblast cells. The maternal KIR genes and their fetal ligands are highly variable, so different KIR/HLA-C genetic combinations occur in each pregnancy. Some women only possess inhibitory KIR genes, whereas other women also express activating KIR genes...
September 5, 2016: Reproductive Biomedicine Online
Farhad Shahsavar, Shaghayegh Mapar, Seyyed Amir Yasin Ahmadi
Multiple sclerosis (MS) is a disease in which we can recognize destruction of the myelin that is around nerve cells of brain and spinal cord called as oligodendrocytes. Both genetic and environmental factors play roles in MS. One of these genes is the killer-cell immunoglobulin-like receptor (KIR) which expressed on surface of natural killer cells (NKs). These genes have loci (not locus) in human genome, so they inherit as haplotypes. The results of previous studies show that different genes of KIR may affect both susceptibility and resistance to such autoimmune disorders that their pathogenesis in MS is still unclear...
December 2016: Genomics Data
Gretchen A Hoff, Johannes C Fischer, Katharine Hsu, Sarah Cooley, Jeffrey S Miller, Tao Wang, Michael Haagenson, Stephen Spellman, Stephanie J Lee, Markus Uhrberg, Jeffrey M Venstrom, Michael R Verneris
Natural Killer (NK) cells are important in graft versus leukemia responses following hematopoietic cell transplantation (HCT). A variety of surface receptors dictate NK cell function, including killer immunoglobulin receptor (KIR) recognition of HLA-C. Previous single center studies show that HLA-C epitopes, designated C1 and C2, were associated with allogeneic-HCT outcomes; specifically recipients homozygous for the C1 epitope (C1/C1) experienced a survival benefit. Additionally, mismatching at HLA-C was beneficial in recipients possessing at least one C2 allele, while the opposite was true for homozygous C1 (C1/C1) recipients where HLA-C mismatching resulted in worse outcomes...
October 13, 2016: Biology of Blood and Marrow Transplantation
Seçil Arslansoyu Çamlar, Mustafa Kır, Ceyda Aydoğan, Şebnem Yılmaz Bengoa, Mehmet Atilla Türkmen, Alper Soylu, Salih Kavukçu
No abstract text is available yet for this article.
September 2016: Türk Pediatri Arşivi
Gamze Isitman, Alexandra Tremblay-McLean, Irene Lisovsky, Julie Bruneau, Bertrand Lebouché, Jean-Pierre Routy, Nicole F Bernard
Natural Killer (NK) cell education, which requires the engagement of inhibitory NK cell receptors (iNKRs) by their ligands, is important for generating self-tolerant functional NK cells. While the potency of NK cell education is directly related to their functional potential upon stimulation with HLA null cells, the influence of NK cell education on the potency of the antibody dependent cellular cytotoxicity (ADCC) function of NK cells is unclear. ADCC occurs when the Fc portion of an immunoglobulin G antibody bridges the CD16 Fc receptor on NK cells and antigen on target cells, resulting in NK cell activation, cytotoxic granule release, and target cell lysis...
2016: PloS One
Cynthia Vierra-Green, David Roe, Jyothi Jayaraman, John Trowsdale, James Traherne, Rui Kuang, Stephen Spellman, Martin Maiers
The killer cell immunoglobulin-like receptors (KIR) mediate human natural killer (NK) cell cytotoxicity via activating or inhibiting signals. Although informative and functional haplotype patterns have been reported, most genotyping has been performed at resolutions that are structurally ambiguous. In order to leverage structural information given low-resolution genotypes, we performed experiments to quantify the effects of population variations, reference haplotypes, and genotyping resolutions on population-level haplotype frequency estimations as well as predictions of individual haplotypes...
2016: PloS One
Cumhur Selcuk Topal, Gözde Kır, Taner Daş, Billur Sarbay, Muzaffer İlkay Tosun
Metastatic bladder tumors constitute <5% of all bladder tumors and metastatic malignant melanoma of the urinary bladder is very rare. We present a case report of a metastatic malignant melanoma of the urinary bladder. A 70-year-old woman without any apparent significant clinical history was admitted to the Department of Urology for gross hematuria. Microscopic findings of the transurethral resection specimen revealed fascicles, sheets, and diffuse areas composed of oval and fusiform cells with focal pigmentation...
October 2016: Indian Journal of Pathology & Microbiology
Daxu Li, Rong Chen, Shin-Ho Chung
Tertiapin (TPN), a short peptide isolated from the venom of the honey bee, is a potent and selective blocker of the inward rectifier K(+) (Kir) channel Kir3.2. Here we examine in atomic detail the binding mode of TPN to Kir3.2 using molecular dynamics, and deduce the key residue in Kir3.2 responsible for TPN selectivity. The binding of TPN to Kir3.2 is stable when the side chain of either Lys16 (TPN(K16)-Kir3.2) or Lys17 (TPN(K17)-Kir3.2) of the toxin protrudes into the channel pore. However, the binding affinity calculated from only TPN(K17)-Kir3...
September 30, 2016: Biophysical Chemistry
Yan Wu, Meng-Yu He, Jian-Kui Ye, Shu-Ying Ma, Wen Huang, Yong-Yue Wei, Hui Kong, Hong Wang, Xiao-Ning Zeng, Wei-Ping Xie
Accumulating data, including those from our laboratory, have shown that the opening of ATP-sensitive potassium channels (KATP ) plays a protective role in pulmonary vascular diseases (PVD). As maintainers of the endothelial framework, endothelial colony-forming cells (ECFCs) are considered excellent candidates for vascular regeneration in cases of PVD. Although KATP openers (KCOs) have been demonstrated to have beneficial effects on endothelial cells, the impact of KATP on ECFC function remains unclear. Herein, this study investigated whether there is a distribution of KATP in ECFCs and what role KATP play in ECFC modulation...
October 6, 2016: Journal of Cellular and Molecular Medicine
Daniele Kazue Sugioka, Carlos Eduardo Ibaldo Gonçalves, Maria da Graça Bicalho
BACKGROUND: Since the discovery of specific histocompatibility, literature has associated genes involved in the immune response, like the Human Leucocyte Antigen (HLA), with a better prognosis in transplantation. However, other non-HLA genes may also influence the immune process, such as the genes encoding the immunoglobulin-like receptors of natural killer cells (KIRs). The discovery that NK cell KIR receptors interact with conservative epitopes (C1, C2, Bw4) presented in HLA class I molecules that are genetically polymorphic, also observed in KIR genes, led to the investigation of the relevance of the KIR system to hematopoietic stem cell transplant...
2016: BMC Hematology
B Erer, M Takeuchi, D Ustek, I Tugal-Tutkun, E Seyahi, Y Özyazgan, J Duymaz-Tozkir, A Gül, D L Kastner, E F Remmers, M J Ombrello
The Behçet's disease (BD)-associated human leukocyte antigen (HLA) allele, HLA-B*51 (B*51), encodes a ligand for a pair of allelic killer immunoglobulin-like receptors (KIR) present on cytotoxic cells-KIR3DL1, which inhibits their cytotoxicity, and KIR3DS1, which activates their cytotoxic activity. We tested whether KIR-regulated mechanisms contribute to BD by testing for association of KIR3DL1/KIR3DS1 genotypes with disease in 1799 BD patients and 1710 healthy controls from Turkey, as well as in different subsets of individuals with HLA-type-defined ligands for the KIR3D receptors...
October 6, 2016: Genes and Immunity
Chang He, Cheng-Rong Yu, Mary J Mattapallil, Lin Sun, Joseph Larkin Iii, Charles E Egwuagu
Uveitis is a potentially sight-threatening disease characterized by repeated cycles of remission and recurrent inflammation. The JAK/STAT pathway regulates the differentiation of pathogenic Th1 and Th17 cells that mediate uveitis. A SOCS1 mimetic peptide (SOCS1-KIR) that inhibits JAK2/STAT1 pathways has recently been shown to suppress experimental autoimmune uveitis (EAU). However, it is not clear whether SOCS1-KIR ameliorated uveitis by targeting JAK/STAT pathways of pathogenic lymphocytes or via inhibition of macrophages and antigen-presenting cells that also enter the retina during EAU...
2016: Mediators of Inflammation
Hai M Nguyen, Eva M Grössinger, Makoto Horiuchi, Kyle W Davis, Lee-Way Jin, Izumi Maezawa, Heike Wulff
Microglia are highly plastic cells that can assume different phenotypes in response to microenvironmental signals. Lipopolysaccharide (LPS) and interferon-γ (IFN-γ) promote differentiation into classically activated M1-like microglia, which produce high levels of pro-inflammatory cytokines and nitric oxide and are thought to contribute to neurological damage in ischemic stroke and Alzheimer's disease. IL-4 in contrast induces a phenotype associated with anti-inflammatory effects and tissue repair. We here investigated whether these microglia subsets vary in their K(+) channel expression by differentiating neonatal mouse microglia into M(LPS) and M(IL-4) microglia and studying their K(+) channel expression by whole-cell patch-clamp, quantitative PCR and immunohistochemistry...
October 3, 2016: Glia
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