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https://www.readbyqxmd.com/read/28100681/lfa-1-activation-in-nk-cells-and-their-subsets-influence-of-receptors-maturation-and-cytokine-stimulation
#1
Doris Urlaub, Kristine Höfer, Martha-Lena Müller, Carsten Watzl
The integrin LFA-1 is essential for efficient activation and for cytotoxicity of NK cells because it initiates the assembly of the immunological synapse and mediates firm adhesion to the target. LFA-1 is also needed to polarize the cytotoxic machinery of the NK cell toward the target cell. The binding affinity and avidity of integrins can be regulated via inside-out signals from other receptors. In this article, we investigate the signals necessary to activate LFA-1 in human NK cells. Our data show that LFA-1 has a low ligand-binding activity in resting human NK cells, but it can be stimulated by triggering activating receptors, such as 2B4 or CD16, or by coactivation of different receptor combinations...
January 18, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28099143/desirable-cytolytic-immune-effector-cell-recruitment-by-interleukin-15-dendritic-cells
#2
Heleen H Van Acker, Ottavio Beretta, Sébastien Anguille, Lien De Caluwé, Angela Papagna, Johan M Van den Bergh, Yannick Willemen, Herman Goossens, Zwi N Berneman, Viggo F Van Tendeloo, Evelien L Smits, Maria Foti, Eva Lion
Success of dendritic cell (DC) therapy in treating malignancies is depending on the DC capacity to attract immune effector cells, considering their reciprocal crosstalk is partially regulated by cell-contact-dependent mechanisms. Although critical for therapeutic efficacy, immune cell recruitment is a largely overlooked aspect regarding optimization of DC vaccination. In this paper we have made a head-to-head comparison of interleukin (IL)-15-cultured DCs and conventional IL-4-cultured DCs with regard to their proficiency in the recruitment of (innate) immune effector cells...
January 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28093832/il-15-deficient-mice-develop-enhanced-allergic-responses-to-airway-allergen-exposure
#3
Clinton B Mathias, Craig M Schramm, Linda A Guernsey, Carol A Wu, Stephanie H Polukort, Jeffrey Rovatti, Jennifer Ser-Dolansky, Eric Secor, Sallie S Schneider, Roger S Thrall, Hector L Aguila
BACKGROUND: Interleukin-15 is a pleiotropic cytokine that is critical for the development and survival of multiple hematopoietic lineages. Mice lacking IL-15 have selective defects in populations of several pro-allergic immune cells including natural killer (NK) cells, NKT cells, and memory CD8(+) T cells. We therefore hypothesized that IL-15(-/-) mice will have reduced inflammatory responses during the development of allergic airway disease (AAD). OBJECTIVE: To determine whether IL-15(-/-) mice have attenuated allergic responses in a mouse model of AAD...
January 17, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28092865/investigations-on-the-immunosuppressive-activity-of-derivatives-of-mycophenolic-acid-in-immature-dendritic-cells
#4
Dorota Iwaszkiewicz-Grzes, Grzegorz Cholewinski, Agata Kot-Wasik, Piotr Trzonkowski, Krystyna Dzierzbicka
The main activity of mycophenolic acid 1 (MPA) and its analogs is the inhibition of proliferation of T cells. Here, we hypothesized that MPA and its conjugates inhibits also the activity of antigen-presenting cells (APC) including dendritic cells (DCs). We tested the effect of novel amino acid derivatives of MPA and conjugates of MPA with acridines/acridones on DCs by flow cytometry, ELISA and MLR assay. Both acridines/acridone derivatives could inhibit the maturation of DC, as shown by the decreased expression of B7 family receptors...
January 13, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28090796/impact-of-c-rel-inhibition-of-cord-blood-derived-b-t-and-nk-cells
#5
Shirin Fallahi, Seyede Momeneh Mohammadi, Hamid Tayefi Nasrabadi, Alireza Alihemmati, Naser Samadi, Sanaz Gholami, Dariush Shanehbandi, Hojjatollah Nozad Charoudeh
The c-Rel transcription factor is a unique member of the nuclear factor (NF)-κB family that has a role in curtailing the proliferation, differentiation, cytokine production, and overall activity of B- and T-cells. In addition, c-Rel is a key regulator of apoptosis in that it influences the expression of anti-apoptotic genes such as Bcl-2 and Bcl-xL; conversely, inhibition of c-Rel increases cell apoptosis. To better understand the relationship between c-Rel expression and effects on B- and T-cell expansion, the current study evaluated c-Rel expression in cord blood mononuclear cells...
January 16, 2017: Journal of Immunotoxicology
https://www.readbyqxmd.com/read/28074436/intrafollicular-inflammatory-cytokines-but-not-steroid-hormone-concentrations-are-increased-in-naturally-matured-follicles-of-women-with-proven-endometriosis
#6
Gengxiang Wu, N A Bersinger, M D Mueller, M von Wolff
PURPOSE: The aim of this study was to assess whether the intrafollicular cytokine profile in naturally developed follicles is different in women with endometriosis, possibly explaining the lower reproductive outcome in endometriosis patients. METHODS: A matched case-control study was conducted at a university-based infertility and endometriosis centre. The study population included 17 patients with laparoscopically and histologically confirmed endometriosis (rAFS stages II-IV), each undergoing one natural cycle IVF (NC-IVF) treatment cycle between 2013 and 2015, and 17 age-matched NC-IVF women without diagnosed endometriosis (control group)...
January 10, 2017: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/28069426/impaired-nk-cell-functions-in-patients-with-stat1-gain-of-function-mutations
#7
Giovanna Tabellini, Donatella Vairo, Omar Scomodon, Nicola Tamassia, Rosalba Monica Ferraro, Ornella Patrizi, Sara Gasperini, Annarosa Soresina, Giuliana Giardino, Claudio Pignata, Vassilios Lougaris, Alessandro Plebani, Laura Dotta, Marco A Cassatella, Silvia Parolini, Raffaele Badolato
BACKGROUND: Gain-of-function (GOF) mutations affecting the coiled-coil domain or the DNA-binding domain of the Signal Transducer and Activator of Transcription 1 (STAT1) cause chronic mucocutaneous candidiasis disease (CMCD). This condition is characterized by fungal and bacterial infections due to impaired generation of Th17 cells; meanwhile some CMCD patients may also develop viral or intracellular pathogens infections. OBJECTIVE: To Investigate the effect of GOF-STAT1 mutations on functioning of Natural Killer (NK) cells...
January 6, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28053237/highly-selective-cleavage-of-cytokines-and-chemokines-by-the-human-mast-cell-chymase-and-neutrophil-cathepsin-g
#8
Zhirong Fu, Michael Thorpe, Rahel Alemayehu, Ananya Roy, Jukka Kervinen, Lawrence de Garavilla, Magnus Åbrink, Lars Hellman
Human mast cell chymase (HC) and human neutrophil cathepsin G (hCG) show relatively similar cleavage specificities: they both have chymotryptic activity but can also cleave efficiently after leucine. Their relatively broad specificity suggests that they may cleave almost any substrate if present in high enough concentrations or for a sufficiently long time. A number of potential substrates have been identified for these enzymes and, recently, these enzymes have also been implicated in regulating cytokine activity by cleaving numerous cytokines and chemokines...
January 4, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28052005/bortezomib-augments-lymphocyte-stimulatory-cytokine-signaling-in-the-tumor-microenvironment-to-sustain-cd8-t-cell-antitumor-function
#9
Samuel T Pellom, Duafalia F Dudimah, Menaka C Thounaojam, Roman V Uzhachenko, Ashutosh Singhal, Ann Richmond, Anil Shanker
Tumor-induced immune tolerance poses a major challenge for therapeutic interventions aimed to manage cancer. We explored approaches to overcome T-cell suppression in murine breast and kidney adenocarcinomas, and lung fibrosarcoma expressing immunogenic antigens. We observed that treatment with a reversible proteasome inhibitor bortezomib (1 mg/kg body weight) in tumor-bearing mice significantly enhanced the expression of lymphocyte-stimulatory cytokines IL-2, IL-12, and IL-15. Notably, bortezomib administration reduced pulmonary nodules of mammary adenocarcinoma 4T1...
December 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/28049849/cd4-t-cell-cytokines-synergize-to-induce-proliferation-of-malignant-and-nonmalignant-innate-intraepithelial-lymphocytes
#10
Yvonne M C Kooy-Winkelaar, Dagmar Bouwer, George M C Janssen, Allan Thompson, Martijn H Brugman, Frederike Schmitz, Arnoud H de Ru, Tom van Gils, Gerd Bouma, Jon J van Rood, Peter A van Veelen, M Luisa Mearin, Chris J Mulder, Frits Koning, Jeroen van Bergen
Refractory celiac disease type II (RCDII) is a severe complication of celiac disease (CD) characterized by the presence of an enlarged clonal population of innate intraepithelial lymphocytes (IELs) lacking classical B-, T-, and natural killer (NK)-cell lineage markers (Lin(-)IELs) in the duodenum. In ∼50% of patients with RCDII, these Lin(-)IELs develop into a lymphoma for which no effective treatment is available. Current evidence indicates that the survival and expansion of these malignant Lin(-)IELs is driven by epithelial cell-derived IL-15...
January 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28049094/aryl-hydrocarbon-receptor-activation-modulates-cd8%C3%AE-%C3%AE-tcr%C3%AE-%C3%AE-iels-and-suppression-of-colitis-manifestations-in-mice
#11
Weigang Chen, Aimin Pu, Baifa Sheng, Zhicao Zhang, Liangzi Li, Zhongze Liu, Qimeng Wang, Xiang Li, Yuanhang Ma, Min Yu, Lihua Sun, Yuan Qiu, Hua Yang
BACKGROUND: This research is dedicated to investigating the effects and potential mechanism of action of the aryl hydrocarbon receptor on the intestinal mucosal immune system in dextran sulfate sodium (DSS)-induced colitis. METHODS: Colitis was induced by the administration of 3% DSS to wild-type C57BL/6J mice for 7days. 6-formylindolo(3, 2-b)carbazole (FICZ), an endogenous agonist of the aryl hydrocarbon receptor (AhR), was given intraperitoneally on a daily basis beginning 2days after the start of DSS administration...
December 31, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28043029/cd4-il-21-t-cells-are-correlated-with-regulatory-t-cells-and-il-21-promotes-regulatory-t-cells-survival-during-hiv-infection
#12
Zi-Ning Zhang, Li-Xin Bai, Ya-Jing Fu, Yong-Jun Jiang, Hong Shang
INTRODUCTION: IL-21 enhances T and natural killer cells survival and antiviral functions without promoting T cell activation during HIV infection, which makes it a better adjuvant in anti-HIV immunotherapy. Due to the pleiotropy and redundancy of cytokines, it is vital to have a comprehensive knowledge of the role of IL-21 in the regulation of immune responses. Regulatory T cells (Tregs) play an important role in immune regulation and are a determinant of immune therapeutic efficacy in certain circumstances...
December 30, 2016: Cytokine
https://www.readbyqxmd.com/read/28035546/disequilibrium-in-the-cd8-cd28-cd8-cd28-t-lymphocyte-balance-is-related-to-prognosis-in-rats-with-trinitrobenzenesulfonic-acid-induced-colitis
#13
Shixue Dai, Hongxiang Gu, Qianyi Lin, Tiaosi Xing, Minhua Chen, Tao Zhong, Gang Wu, Yanling Feng, Hongbo Liu, Yong Gao, Hongjian Jian, Minhai Zhang, Hongmei Mo, Huanjie Zhu, Dongsheng Chen, Jun Xu, Ying Zou, Honggang Chi, Yuzhen Zhu
PURPOSE: The CD8(+)CD28(+)/CD8(+)CD28(-) T lymphocyte balance is vital for human ulcerative colitis (UC) but has not been defined in experimental colitis. This investigation will try to identify the changes that occur in the CD8(+)CD28(+)/CD8(+)CD28(-) T lymphocyte balance during the progression of trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. METHODS: The frequencies of blood CD8(+)CD28(+) and CD8(+)CD28(-) T lymphocytes were detected in the rats belonging to the normal, model, and treated groups on five days using flow cytometry...
December 29, 2016: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28031720/atypical-aleukemic-presentation-of-large-granular-lymphocytic-leukemia-a-case-report
#14
Cristina Bagacean, Adrian Tempescul, Mariana Patiu, Bogdan Fetica, Horia Bumbea, Mihnea Zdrenghea
Large granular lymphocytic leukemia (LGLL) is a rare lymphoproliferative disorder of transformed natural killer or T-cells attributed to chronic exposure to the proinflammatory cytokine IL-15. Diagnosis of the majority of T-cell LGLL is established by documenting clonal large granular lymphocytes (LGLs) in peripheral blood, by morphology and immunophenotype. The proteasome inhibitor bortezomib is known to target molecular pathways downstream of the IL-15 receptor signaling and has been proposed as a therapy in these patients...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28031340/il-15-enables-septic-shock-by-maintaining-nk-cell-integrity-and-function
#15
Yin Guo, Liming Luan, Naeem K Patil, Jingbin Wang, Julia K Bohannon, Whitney Rabacal, Benjamin A Fensterheim, Antonio Hernandez, Edward R Sherwood
Interleukin 15 is essential for the development and differentiation of NK and memory CD8(+) (mCD8(+)) T cells. Our laboratory previously showed that NK and CD8(+) T lymphocytes facilitate the pathobiology of septic shock. However, factors that regulate NK and CD8(+) T lymphocyte functions during sepsis are not well characterized. We hypothesized that IL-15 promotes the pathogenesis of sepsis by maintaining NK and mCD8(+) T cell integrity. To test our hypothesis, the pathogenesis of sepsis was assessed in IL-15-deficient (IL-15 knockout, KO) mice...
December 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28013013/a-canine-model-of-chronic-graft-versus-host-disease
#16
Scott S Graves, Andrew Rezvani, George Sale, Diane Stone, Maura Parker, Steven Rosinski, Michele Spector, Bruce Swearingen, Leslie Kean, Rainer Storb
In long-term survivors of allogeneic hematopoietic cell transplantation (HCT), chronic graft-versus-host disease (GVHD) is the major cause of morbidity and mortality and a major determinant of quality of life. Chronic GVHD responds poorly to current immunosuppressive drugs, and while T cell depletion may be preventive, this gain is offset by increased relapse rates. A significant impediment to progress in treating chronic GVHD has been the limitations of existing animal models. The goal of this study was to develop a reproducible comprehensive model of chronic GVHD in the dog...
December 21, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28012777/sequential-administration-of-a-mva-based-muc1-cancer-vaccine-and-the-tlr9-ligand-litenimod-li28-improves-local-immune-defense-against-tumors
#17
Emmanuelle Schaedler, Christelle Remy-Ziller, Julie Hortelano, Nadine Kehrer, Marie-Christine Claudepierre, Tanja Gatard, Christopher Jakobs, Xavier Préville, Antoine F Carpentier, Karola Rittner
TG4010 is an immunotherapeutic vaccine based on Modified Vaccinia virus Ankara (MVA) encoding the human tumor-associated antigen MUC1 and human IL-2. In combination with first-line standard of care chemotherapy in advanced metastatic non-small-cell lung cancer (NSCLC), repeated subcutaneous injection of TG4010 improved progression-free survival in phase 2b clinical trials. In preclinical tumor models, MVATG9931, the research version of TG4010, conferred antigen-specific responses against the weak antigen human MUC1...
December 21, 2016: Vaccine
https://www.readbyqxmd.com/read/28011147/interleukin-15-is-associated-with-severity-and-mortality-in-stevens-johnson-syndrome-toxic-epidermal-necrolysis
#18
Shih-Chi Su, Maja Mockenhaupt, Pierre Wolkenstein, Ariane Dunant, Sabine Le Gouvello, Chun-Bing Chen, Olivier Chosidow, Laurence Valeyrie-Allanore, Teresa Bellon, Peggy Sekula, Chuang-Wei Wang, Martin Schumacher, Sylvia H Kardaun, Shuen-Iu Hung, Jean-Claude Roujeau, Wen-Hung Chung
Early diagnosis and prognosis monitoring for Stevens-Johnson syndrome (SJS)/ toxic epidermal necrolysis (TEN) still remain a challenge. This study aims to explore any cytokine/chemokine with prognostic potential in SJS/TEN. Through screening a panel of 28 serological factors, IL-6, IL-8, IL-15, TNF-α, and granulysin were upregulated in SJS/TEN patients and selected for the further validation in total 155 SJS/TEN patients, including 77 from Taiwan and 78 from RegiSCAR (the Registry of Severe Cutaneous Adverse Reactions)...
December 20, 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27998802/janus-kinase-inhibition-for-immunosuppression-in-solid-organ-transplantation-is-there-a-role-in-complex-immunologic-challenges
#19
REVIEW
Cody A Moore, Carlo J Iasella, Raman Venkataramanan, Fadi G Lakkis, Randall B Smith, John F McDyer, Adriana Zeevi, Christopher R Ensor
Inhibition of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway for immunosuppression in solid organ transplantation is appealing due to its specificity for immune cell function, particularly for JAK3. This is due to its unique association with only the common gamma chain (γc). The γc is an appealing immunosuppression target in transplantation because of the critically important lymphokines that act at it, including IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Tofacitinib was initially purported to selectively inhibit solely JAK3, but subsequent analyses have also demonstrated its activity at the other members of the JAK family...
December 18, 2016: Human Immunology
https://www.readbyqxmd.com/read/27995612/-inflamm-aging-influences-immune-cell-survival-factors-in-human-bone-marrow
#20
Luca Pangrazzi, Andreas Meryk, Erin Naismith, Rafal Koziel, Julian Lair, Martin Krismer, Klemens Trieb, Beatrix Grubeck-Loebenstein
The bone marrow (BM) plays a key role in the long-term maintenance of immunological memory. However, the impact of aging on the production of survival factors for effector/memory T cells and plasma cells in the human BM has not been studied. We now show that the expression of molecules involved in the maintenance of immunological memory in the human BM changes with age. While IL-15, which protects potentially harmful CD8(+) CD28(-) senescent T cells, increases, IL-7 decreases. IL-6, which may synergize with IL-15, is also overexpressed...
December 19, 2016: European Journal of Immunology
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