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Iris C J Blijdorp, Silvia Menegatti, Leonike J J Van Mens, Marleen G H van de Sand, Sijia Chen, Hulda S Hreggvidsdottir, Troy Noordenbos, Talia E Latuhihin, Jochem H Bernink, Hergen Spits, Lars Rogge, Dominique L P Baeten, Nataliya G Yeremenko
OBJECTIVE: Clinical trials of the anti-IL-17A antibody secukinumab demonstrated a crucial role of the IL-17A cytokine in the pathogenesis of spondyloarthritis (SpA), however its cellular source in this condition remains controversial. Group 3 innate lymphoid cells (ILC3s) have been recently identified in a number of different tissues as potent producers of proinflamatory cytokines, including IL-17A and IL-22. In this study we set out to characterize the presence and composition of ILCs and investigate whether these cells are an important source of IL-17A in the synovial tissue of patients with SpA...
September 27, 2018: Arthritis & Rheumatology
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
Silvia Gaggero, Maurizio Bruschi, Andrea Petretto, Monica Parodi, Genny Del Zotto, Chiara Lavarello, Carola Prato, Laura Santucci, Alessandra Barbuto, Cristina Bottino, Giovanni Candiano, Alessandro Moretta, Massimo Vitale, Lorenzo Moretta, Claudia Cantoni
The release of soluble ligands of activating Natural Killer (NK) cell receptors may represent a regulatory mechanism of NK cell function both in physiologic and in pathologic conditions. Here, we identified the extracellular matrix protein Nidogen-1 (NID1) as a ligand of NKp44, an important activating receptor expressed by activated NK cells. When released as soluble molecule, NID1 regulates NK cell function by modulating NKp44-induced IFN-γ production or cytotoxicity. In particular, it also modulates IFN-γ production induced by Platelet-Derived Growth Factor (PDGF)-DD following NKp44 engagement...
2018: Oncoimmunology
Samantha McQuaid, Sinead Loughran, Patrick Power, Paula Maguire, Dermot Walls, Maria Grazia Cusi, Claes Orvell, Patricia Johnson
No abstract text is available yet for this article.
September 2018: Journal of General Virology
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
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
Robert J Canter, William J Murphy
Immunotherapy is rapidly becoming the fourth arm of cancer treatment, and breakthrough successes have been observed in multiple malignancies. However, despite the potential for impressive anti-tumor effects, on average, only 25% of patients respond, and barriers clearly remain. Hence, uncovering innovative ways to apply immunotherapy and overcome immune resistance remains an unmet need in immuno-oncology. Natural killer (NK) cells are an attractive candidate for extending the promise of immunotherapy, although success to date has been largely limited to hematological cancers...
August 7, 2018: Journal for Immunotherapy of Cancer
Sylvain Audia, Thomas Moulinet, Marion Ciudad-Bonté, Maxime Samson, Olivier Facy, Pablo Ortega-Deballon, Philippe Saas, Bernard Bonnotte
Innate lymphoid cells (ILCs) have been characterized as innate immune cells capable to modulate the immune response in the mucosae. Human ILCs have been rarely described in secondary lymphoid organs except in tonsils. Moreover, their function and phenotype in human secondary lymphoid organs during autoimmune diseases have never been studied. We took advantage of splenectomy as a treatment of immune thrombocytopenia (ITP) to describe and compare splenic ILC from 18 ITP patients to 11 controls. We first confirmed that ILC3 represented the most abundant ILC subset in human non-inflamed spleens, accounting for 90% of total ILC, and that they were mostly constituted of NKp44- cells...
September 2018: Journal of Autoimmunity
Maria Giovanna Desimio, Erica Giuliani, Angelo Salvatore Ferraro, Gaspare Adorno, Margherita Doria
In the attempt of purging the HIV-1 reservoir through the "shock-and-kill" strategy, it is important to select latency-reversing agents (LRAs) devoid of deleterious effects on the antiviral function of immune effector cells. Here, we investigated two LRAs with PKC agonist activity, prostratin (PRO) and bryostatin-1 (BRY), for their impact on the function of natural killer (NK) cells, the major effectors of innate immunity whose potential in HIV-1 eradication has emerged in recent clinical trials. Using NK cells of healthy donors, we found that exposure to either PRO or BRY potently activated NK cells, resulting in upmodulation of NKG2D and NKp44 activating receptors and matrix metalloprotease-mediated shedding of CD16 receptor...
2018: Frontiers in Immunology
Becker Meng-Po Law, Ray Wilkinson, Xiangju Wang, Katrina Kildey, Mae Lindner, Kenneth Beagley, Helen Healy, Andrew J Kassianos
Background: γδ T cells are effector lymphocytes recognized as key players during chronic inflammatory processes. Mouse studies suggest a pathological role for γδ T cells in models of kidney disease. Here we evaluated γδ T cells in human native kidneys with tubulointerstitial fibrosis, the pathological hallmark of chronic kidney disease. Methods: γδ T cells were extracted from human kidney tissue and enumerated and phenotyped by multicolour flow cytometry...
April 20, 2018: Nephrology, Dialysis, Transplantation
Avishai Shemesh, Kiran Kundu, Refael Peleg, Rami Yossef, Irena Kaplanov, Susmita Ghosh, Yana Khrapunsky, Orly Gershoni-Yahalom, Tatiana Rabinski, Adelheid Cerwenka, Roee Atlas, Angel Porgador
Proliferating cell nuclear antigen (PCNA) is considered as a hub protein and is a key regulator of DNA replication, repair, cell cycle control, and apoptosis. PCNA is overexpressed in many cancer types, and PCNA overexpression is correlated with cancer virulence. Membrane-associated PCNA is a ligand for the NKp44 (NCR2) innate immune receptor. The purpose of this study was to characterize the PCNA-binding site within NKp44. We have identified NKp44-derived linear peptide (pep8), which can specifically interact with PCNA and partly block the NKp44-PCNA interaction...
2018: Frontiers in Immunology
Bruno Silva-Santos, Jessica Strid
Natural killer cell receptors (NKRs) are germline-encoded transmembrane proteins that regulate the activation and homeostasis of NK cells as well as other lymphocytes. For γδ T cells, NKRs play critical roles in discriminating stressed (transformed or infected) cells from their healthy counterparts, as proposed in the "lymphoid stress-surveillance" theory. Whereas the main physiologic role is seemingly fulfilled by natural killer group 2 member D, constitutively expressed by γδ T cells, enhancement of their therapeutic potential may rely on natural cytotoxicity receptors (NCRs), like NKp30 or NKp44, that can be induced selectively on human Vδ1+ T cells...
2018: Frontiers in Immunology
Samantha McQuaid, Sinead Loughran, Patrick Power, Paula Maguire, Dermot Walls, Maria Grazia Cusi, Claes Orvell, Patricia Johnson
HPIV3 is a respiratory virus causing airway diseases, including pneumonia, croup, and bronchiolitis, during infancy and childhood. Currently there is no effective vaccine or anti-viral therapy for this virus. Studies have suggested that poor T cell proliferation following HPIV3 infection is responsible for impaired immunological memory associated with this virus. We have previously demonstrated that NK cells mediate regulation of T cell proliferation during HPIV3 infection. Here we add to these studies by demonstrating that the regulation of T cell proliferation during HPIV3 infection is mediated via NK receptors NKp44 and NKp46 and involves the surface glycoprotein haemagglutinin-neuraminidase but not the fusion protein of the virus...
June 2018: Journal of General Virology
M H Abumaree, E Bahattab, A Alsadoun, A Al Dosaimani, F M Abomaray, T Khatlani, B Kalionis, M F El-Muzaini, A O Alawad, A S AlAskar
BACKGROUND: Human decidua parietalis mesenchymal stem/multipotent stromal cells (DPMSCs) have unique phenotypic and functional properties that make them promising candidates for cell-based therapy. Here, we investigated DPMSC interaction with natural killer (NK) cells, and the effects of this interaction on NK cell phenotypic characteristics and functional activities. METHODS: DPMSCs isolated from the decidua parietalis of human fetal membranes were cultured with interleukin (IL)-2-activated and IL-2-unactivated NK cells isolated from healthy human peripheral blood...
April 12, 2018: Stem Cell Research & Therapy
Yuanji Xu, Rui Zhou, Chuanzhong Huang, Mingwei Zhang, Jieyu Li, Jingfeng Zong, Sufang Qiu, Shaojun Lin, Honglin Chen, Yunbin Ye, Jianji Pan
Background: The aberrant expression of surface receptors on immunocytes may represent potential markers of tumor escape for nasopharyngeal carcinoma (NPC). The aim of this study was to investigate the expression of representative receptors on natural killer (NK) cells and NK group 2, member D (NKG2D) on immunocytes in the peripheral blood of patients with NPC. Methods: Patients (n = 64) with NPC prior to initiation of treatment were defined as the study group. Healthy volunteers (n = 31) served as the control group...
March 27, 2018: Asian Pacific Journal of Cancer Prevention: APJCP
Lucía Fernández, Alejandra Leivas, Jaime Valentín, Adela Escudero, Dolores Corral, Raquel de Paz, Maria Vela, David Bueno, Rebeca Rodríguez, Juan Manuel Torres, Mariana Díaz-Almirón, Eduardo López-Collazo, Joaquin Martinez-Lopez, Antonio Pérez-Martínez
BACKGROUND: Cancer immunotherapy involving natural killer (NK) cells has gained interest. Here we report two methods to obtain interleukin (IL)-15-activated NK cells for clinical use. STUDY DESIGN AND METHODS: IL-15-activated NK cell products were obtained after 1) enrichment from healthy haploidentical donors' peripheral blood mononuclear cells (PBMNCs) collected by nonmobilized apheresis by a two-step magnetic procedure, depletion of CD3+ cells followed by selection of CD56+ cells and ex vivo overnight stimulation with IL-15 (NKIL15); and 2) expansion using the K562-mb15-41BBL cell line (NKAE), from autologous PBMNCs from patients with multiple myeloma or expansion from healthy haploidentical PBMNCs obtained from whole blood using the same previous cell line...
June 2018: Transfusion
Giorgio Trinchieri
In addition to exogenous ligands derived from pathogens, natural killer (NK) and other innate cells can recognize endogenous ligands that often act as markers of stress or damage. A recent study reports that one of these receptors, human NKp44, recognizes PDGF-DD, providing a rare example of the recognition of a soluble growth factor as a stress signal. The recognition of PDGF-DD induces the secretion of cytokines with antitumor activity.
May 2018: Trends in Immunology
Kelly E Bowen, Stephen O Mathew, Kathleen Borgmann, Anuja Ghorpade, Porunelloor A Mathew
NK cells play important role in immunity against pathogens and cancer. NK cell functions are regulated by inhibitory and activating receptors binding corresponding ligands on the surface of target cells. NK cells were shown to be recruited to the CNS following several pathological conditions. NK cells could impact CNS physiology by killing glial cells and by secreting IFN-γ. Astrocytes are intimately involved in immunological and inflammatory events occurring in the CNS and reactive astrogliosis is a key feature in HIV-associated neurocognitive disorders...
2018: PloS One
Tina Nham, Sophie M Poznanski, Isabella Y Fan, Mira M Shenouda, Marianne V Chew, Amanda J Lee, Fatemeh Vahedi, Yalda Karimi, Martin Butcher, Dean A Lee, Hal Hirte, Ali A Ashkar
Ovarian cancer (OC) is the leading cause of gynecological cancer-related death in North America. Most ovarian cancer patients (OCPs) experience disease recurrence after first-line surgery and chemotherapy; thus, there is a need for novel second-line treatments to improve the prognosis of OC. Although peripheral blood-derived NK cells are known for their ability to spontaneously lyse tumour cells without prior sensitization, ascites-derived NK cells (ascites-NK cells) isolated from OCPs exhibit inhibitory phenotypes, impaired cytotoxicity and may play a pro-tumourigenic role in cancer progression...
April 2018: Cancer Immunology, Immunotherapy: CII
Alexander D Barrow, Melissa A Edeling, Vladimir Trifonov, Jingqin Luo, Piyush Goyal, Benjamin Bohl, Jennifer K Bando, Albert H Kim, John Walker, Mary Andahazy, Mattia Bugatti, Laura Melocchi, William Vermi, Daved H Fremont, Sarah Cox, Marina Cella, Christian Schmedt, Marco Colonna
Many tumors produce platelet-derived growth factor (PDGF)-DD, which promotes cellular proliferation, epithelial-mesenchymal transition, stromal reaction, and angiogenesis through autocrine and paracrine PDGFRβ signaling. By screening a secretome library, we found that the human immunoreceptor NKp44, encoded by NCR2 and expressed on natural killer (NK) cells and innate lymphoid cells, recognizes PDGF-DD. PDGF-DD engagement of NKp44 triggered NK cell secretion of interferon gamma (IFN)-γ and tumor necrosis factor alpha (TNF-α) that induced tumor cell growth arrest...
January 25, 2018: Cell
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