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https://www.readbyqxmd.com/read/28727766/clinical-implications-of-the-novel-cytokine-il-38-expressed-in-lung-adenocarcinoma-possible-association-with-pd-l1-expression
#1
Kazuki Takada, Tatsuro Okamoto, Masaki Tominaga, Koji Teraishi, Takaki Akamine, Shinkichi Takamori, Masakazu Katsura, Gouji Toyokawa, Fumihiro Shoji, Masaki Okamoto, Yoshinao Oda, Tomoaki Hoshino, Yoshihiko Maehara
Interleukin (IL)-38, a novel member of the IL-1 cytokine family, is homologous to IL-1 receptor antagonist (IL-1Ra) and IL-36Ra, and has been reported to act as an antagonist. IL-38 expression is found in tonsil, placenta, and spleen, and recent studies suggest an association between IL-38 and autoimmune diseases. However, whether IL-38 plays a role in carcinogenesis or cancer growth is unclear. In the present study, we identified increases in IL-38 expression by immunohistochemistry in multiple types of cancer cells...
2017: PloS One
https://www.readbyqxmd.com/read/28727763/loss-of-receptor-activity-modifying-protein-2-in-mice-causes-placental-dysfunction-and-alters-pth1r-regulation
#2
Mahita Kadmiel, Brooke C Matson, Scott T Espenschied, Patricia M Lenhart, Kathleen M Caron
Receptor activity-modifying protein 2 (Ramp2) is a single-pass transmembrane protein that heterodimerizes with several family B G-protein coupled receptors to alter their function. Ramp2 has been primarily characterized in association with calcitonin receptor-like receptor (Calcrl, CLR), forming the canonical receptor complex for the endocrine peptide adrenomedullin (Adm, AM). However, we previously demonstrated that Ramp2+/- female mice display a constellation of endocrine-related phenotypes that are distinct from those of Adm+/- and Calcrl+/- mice, implying that RAMP2 has physiological functions beyond its canonical complex...
2017: PloS One
https://www.readbyqxmd.com/read/28727113/feed-withdrawal-and-transportation-effects-on-salmonella-enterica-levels-in-market-weight-pigs
#3
S D Eicher, M H Rostagno, D C Lay
Feed withdrawal and transport commonly occur together in pigs. Objectives of this study were to determine if these preslaughter stressors, feed withdrawal and transportation, affect the levels of , stress hormone concentrations, and immune functions in infected market pigs. A 2 × 2 factorial analysis of a randomized complete block design with feed withdrawal and transport as fixed effects was used. Sixty market-weight pigs were individually inoculated with serovar Typhimurium. The experiment was replicated 3 times (blocking factor) with 20 pigs per replicate...
July 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28727040/genome-wide-association-studies-and-meta-analysis-reveal-novel-quantitative-trait-loci-and-pleiotropic-loci-for-swine-head-related-traits
#4
H Chen, T Huang, Z Zhang, B Yang, C Jiang, J Wu, Z Zhou, H Zheng, W Xin, M Huang, M Zhang, C Chen, J Ren, H Ai, L Huang
The pig is an important domestic animal that provides a larger amount of meat and serves as a biomedical animal model for human. Head and facial features are closely linked to identity recognition in mammal communication. To uncover the genetic architecture of swine head and facial features, we constructed 5 experimental pig populations and accurately measured 10 traits related to head and facial features, for which genome-wide association studies and meta-analysis were later carried out. As a result, we identified a total of 24 loci harboring 437 SNP on 8 swine chromosomes (SSC) that surpassed suggestively significant levels, of which 17 loci on 6 chromosomes exceeded the 5% genome-wide significance thresholds...
June 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28726981/triennial-growth-and-development-symposium-factors-influencing-bovine-intramuscular-adipose-tissue-development-and-cellularity
#5
E Albrecht, L Schering, Y Liu, K Komolka, C Kühn, K Wimmers, T Gotoh, S Maak
Appearance, distribution, and amount of intramuscular fat (IMF), often referred to as marbling, are highly variable and depend on environmental and genetic factors. On the molecular level, the concerted action of several drivers, including hormones, receptors, transcription factors, etc., determines where clusters of adipocytes arise. Therefore, the aim of future studies remains to identify such factors as biological markers of IMF to increase the ability to identify animals that deposit IMF early in age to increase efficiency of high-quality meat production...
May 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28726773/t-cell-autonomous-death-induced-by-regeneration-of-inert-glucocorticoid-metabolites
#6
Lourdes Rocamora-Reverte, Holger M Reichardt, Andreas Villunger, GJan Wiegers
Glucocorticoids (GC) are essential regulators of T-cell development and function. Activation of the immune system increases systemic adrenal-derived GC levels which downregulate immune activity as part of a negative feedback control system. Increasing evidence shows, however, that GC can also be derived from extra-adrenal sources such as the thymus or intestine, thus providing local control of GC-mediated effects. The thymus reportedly produces GC, but whether thymic epithelial cells or thymocytes produce GC acting either in an autocrine or paracrine fashion is not clear...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28726211/genetic-engineering-of-native-chain-combinations-of-b-cell-repertoires-on-the-surface-of-methylotrophic-yeasts-pichia-pastoris
#7
T V Bobik, E M Shurdova, I V Smirnov, N A Ponomarenko, E N Khurs, V D Knorre, A G Gabibov
We designed genetic constructs for exposing Fab-fragment library of natively paired single cell B-cell receptors on the surface of Pichia pastoris yeast cells. We have previously obtained the A17 antibody in our laboratory [6]. In this study we showed that the newly designed genetic constructs provide a compatible level of A17 antibody Fab fragment on the surface of yeast cells as well as in the case of vectors containing DNA fragments corresponding to each chain of the antibody. The data suggest that the developed approach for constructing immunoglobulin gene libraries is adequate and fully convenient for studying properties of the real human B-lymphocyte repertoire...
July 18, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28725433/macrophage-type-2-differentiation-in-a-patient-with-laryngeal-squamous-cell-carcinoma-and-metastatic-prostate-adenocarcinoma-to-the-cervical-lymph-nodes
#8
Michael C Topf, Madalina Tuluc, Larry A Harshyne, Adam Luginbuhl
BACKGROUND: The tumor microenvironment often polarizes infiltrating macrophages towards a type 2, or M2 phenotype, that is characterized by expression of various cysteine-rich, scavenger receptors, including CD163. The primary function of M2 macrophages is to facilitate wound healing. As such, they are capable of providing metabolic support to a growing tumor, neovascularization, as well as protection from cytotoxic T cells. The tumor microenvironment contains a milieu of secreted factors and vesicles, which in certain circumstances can gain access to lymphatic vessels that drain to local lymph nodes...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28725432/transplanters-drive-cars-to-the-clinic-by-brewing-ice-t-the-moffitt-roadmap
#9
EDITORIAL
Frederick L Locke, Claudio Anasetti
Recent single institution clinical trial successes with anti-CD19 Chimeric Antigen Receptor (CAR) T cell therapy for B cell malignancies attracted significant attention from industry. Our center sought to rapidly and safely bring industry sponsored pivotal trials to our patients and to prepare for additional cell therapy trials in solid and liquid tumors from both industry and our own investigators. We implemented a collaborative cross departmental program to provide clinical care and trial coordination for immune cell therapies...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28725044/cord-blood-nk-cells-engineered-to-express-il-15-and-a-cd19-targeted-car-show-long-term-persistence-and-potent-anti-tumor-activity
#10
E Liu, Y Tong, G Dotti, H Shaim, B Savoldo, M Mukherjee, J Orange, X Wan, X Lu, A Reynolds, M Gagea, P Banerjee, R Cai, M H Bdaiwi, R Basar, M Muftuoglu, L Li, D Marin, W Wierda, M Keating, R Champlin, E Shpall, K Rezvani
Chimeric antigen receptors (CARs) have been used to redirect the specificity of autologous T-cells against leukemia and lymphoma with promising clinical results.(1-3) Extending this approach to allogeneic T-cells is problematic as they carry a significant risk of graft-versus-host disease (GVHD). Natural killer (NK) cells are highly cytotoxic effectors, killing their targets in a non-antigen specific manner without causing GVHD. Cord blood (CB) offers an attractive, allogeneic, off-the-self source of NK cells for immunotherapy...
July 20, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28724955/mushroom-lectin-overcomes-hepatitis-b-virus-tolerance-via-tlr6-signaling
#11
Meina He, Dan Su, Qinghong Liu, Wenjuan Gao, Youmin Kang
Currently, chronic hepatitis B virus (HBV) infection remains a serious public health problem in the world. Recombinant HBV vaccine, as a preventive strategy against HBV infection, generates high antibody level, but it is not effective to activate innate and cellular immunity for chronic HBV infection therapy. Lectins from mushroom are natural and active proteins which have been shown important biological functions. However, little is known about the immunological mechanism engaged by mushroom lectins. Here we report that, lectin from Pleurotus ostreatus (POL) stimulated innate response by activating Toll-like receptor 6 signal pathway of dendritic cells...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724935/histone-deacetylase-3-is-required-for-inkt-cell-development
#12
Puspa Thapa, Sinibaldo Romero Arocha, Ji Young Chung, Derek B Sant'Angelo, Virginia Smith Shapiro
NKT cells are a distinct subset that have developmental requirements that often differ from conventional T cells. Here, we show that NKT-specific deletion of Hdac3 results in a severe reduction in the number of iNKT cells, particularly of NKT1 cells. In addition, there is decreased cytokine production by Hdac3-deficient NKT2 and NKT17 cells. Hdac3-deficient iNKT cells have increased cell death that is not rescued by transgenic expression of Bcl-2 or Bcl-xL. Hdac3-deficient iNKT cells have less Cyto-ID staining and lower LC3A/B expression, indicative of reduced autophagy...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724801/tcr-ligand-dissociation-rate-is-a-robust-and-stable-biomarker-of-cd8-t-cell-potency
#13
Mathilde Allard, Barbara Couturaud, Laura Carretero-Iglesia, Minh Ngoc Duong, Julien Schmidt, Gwennaëlle C Monnot, Pedro Romero, Daniel E Speiser, Michael Hebeisen, Nathalie Rufer
Despite influencing many aspects of T cell biology, the kinetics of T cell receptor (TCR) binding to peptide-major histocompatibility molecules (pMHC) remain infrequently determined in patient monitoring or for adoptive T cell therapy. Using specifically designed reversible fluorescent pMHC multimeric complexes, we performed a comprehensive study of TCR-pMHC off-rates combined with various functional assays on large libraries of self/tumor- and virus-specific CD8+ T cell clones from melanoma patients and healthy donors...
July 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28724795/alx-receptor-ligands-define-a-biochemical-endotype-for-severe-asthma
#14
Isabell Ricklefs, Ioanna Barkas, Melody G Duvall, Manuela Cernadas, Nicole L Grossman, Elliot Israel, Eugene R Bleecker, Mario Castro, Serpil C Erzurum, John V Fahy, Benjamin M Gaston, Loren C Denlinger, David T Mauger, Sally E Wenzel, Suzy A Comhair, Andrea M Coverstone, Merritt L Fajt, Annette T Hastie, Mats W Johansson, Michael C Peters, Brenda R Phillips, Bruce D Levy
BACKGROUND: In health, inflammation resolution is an active process governed by specialized proresolving mediators and receptors. ALX/FPR2 receptors (ALX) are targeted by both proresolving and proinflammatory ligands for opposing signaling events, suggesting pivotal roles for ALX in the fate of inflammatory responses. Here, we determined if ALX expression and ligands were linked to severe asthma (SA). METHODS: ALX expression and levels of proresolving ligands (lipoxin A4 [LXA4], 15-epi-LXA4, and annexin A1 [ANXA1]), and a proinflammatory ligand (serum amyloid A [SAA]) were measured in bronchoscopy samples collected in Severe Asthma Research Program-3 (SA [n = 69], non-SA [NSA, n = 51] or healthy donors [HDs, n = 47])...
July 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28724766/a-unique-t-cell-receptor-amino-acid-sequence-selected-by-htlv-i-tax301-309-specific-cytotoxic-t-cells-in-hla-a24-02-asymptomatic-carriers-and-adult-t-cell-leukemia-lymphoma-patients
#15
Yuko Ishihara, Yukie Tanaka, Seiichiro Kobayashi, Koji Kawamura, Hideki Nakasone, Ayumi Gomyo, Jin Hayakawa, Masaharu Tamaki, Yu Akahoshi, Naonori Harada, Machiko Kusuda, Kazuaki Kameda, Tomotaka Ugai, Hidenori Wada, Kana Sakamoto, Miki Sato, Kiriko Terasako-Saito, Misato Kikuchi, Shun-Ichi Kimura, Aki Tanihara, Shinichi Kako, Kaoru Uchimaru, Yoshinobu Kanda
We previously reported that the T-cell receptor (TCR) repertoire of HTLV-I Tax301-309-specific CD8(+) cytotoxic T-cells (Tax-CTLs) was highly restricted and a particular amino acid sequence motif, "PDR", was conserved among HLA-A*24:02(+) ATL patients who have undergone allogeneic hematopoietic cell transplantation (allo-HSCT). Furthermore, we found that donor-derived PDR+CTLs selectively expanded in ATL long-term HSCT survivors with strong CTL activity against HTLV-I. On the other hand, the TCR repertoires in Tax-CTL of asymptomatic HTLV-I carriers (ACs) remain unclear...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28724573/a-single-dose-of-peripherally-infused-egfrviii-directed-car-t-cells-mediates-antigen-loss-and-induces-adaptive-resistance-in-patients-with-recurrent-glioblastoma
#16
Donald M O'Rourke, MacLean P Nasrallah, Arati Desai, Jan J Melenhorst, Keith Mansfield, Jennifer J D Morrissette, Maria Martinez-Lage, Steven Brem, Eileen Maloney, Angela Shen, Randi Isaacs, Suyash Mohan, Gabriela Plesa, Simon F Lacey, Jean-Marc Navenot, Zhaohui Zheng, Bruce L Levine, Hideho Okada, Carl H June, Jennifer L Brogdon, Marcela V Maus
We conducted a first-in-human study of intravenous delivery of a single dose of autologous T cells redirected to the epidermal growth factor receptor variant III (EGFRvIII) mutation by a chimeric antigen receptor (CAR). We report our findings on the first 10 recurrent glioblastoma (GBM) patients treated. We found that manufacturing and infusion of CAR-modified T cell (CART)-EGFRvIII cells are feasible and safe, without evidence of off-tumor toxicity or cytokine release syndrome. One patient has had residual stable disease for over 18 months of follow-up...
July 19, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28724396/pathogenic-roles-of-cxcl10-signaling-through-cxcr3-and-tlr4-in-macrophages-and-t-cells-relevance-for-arthritis
#17
Jong-Ho Lee, Bongjun Kim, Won Jong Jin, Hong-Hee Kim, Hyunil Ha, Zang Hee Lee
BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by uncontrolled joint inflammation and destruction of bone and cartilage. We previously reported that C-X-C motif chemokine 10 (CXCL10; also called IP-10) has important roles in joint inflammation and bone destruction in arthritis. However, the specific mechanisms by which CXCL10 regulates the recruitment of inflammatory cells and the production of osteoclastogenic cytokines in RA progression are not fully understood...
July 19, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28723925/immunologic-response-to-vaccine-challenge-in-pregnant-ptpn22-r620w-carriers-and-non-carriers
#18
Shelly H Tien, Juliet N Crabtree, Heather L Gray, Erik J Peterson
OBJECTIVES: Influenza infection is a significant cause of respiratory morbidity among pregnant women. Seasonal influenza vaccination engages innate immune receptors to promote protective immunity. A coding polymorphism (R620W) in PTPN22 imparts elevated risk for human infection and autoimmune disease, predisposes to diminished innate immune responses, and associates with reduced immunization responses. We sought to quantify the effects of PTPN22-R620W on humoral and cell-mediated immune responses to the inactivated influenza vaccine among healthy pregnant women...
2017: PloS One
https://www.readbyqxmd.com/read/28723671/qishenyiqi-pill-attenuates-atherosclerosis-by-promoting-regulatory-t-cells-inhibiting-t-helper-17-cells-and-accelerating-cholesterol-excretion
#19
Li Peng, Chong-Shan Lv, Yun Zhao, Shao-Dong Chen, Yang Huang, Da-Wei Lu, Shu-Qiong Huang, Zong-Bao Yang, Lin-Chao Qian, Lei Wen
OBJECTIVE: The aim of this study was to explore potential immunoregulatory mechanisms underlying the suppressive effect on atherosclerosis of QiShenYiQi pill (QSYQ). METHODS AND RESULTS: Male ApoE-/- mice were maintained on a Western-type diet and QSYQ treatment for eight weeks. Determination of atherosclerosis demonstrated that QSYQ attenuated plaque formation and decreased the level of blood low-density lipoproteins-cholesterol. QSYQ treatment did not affect body weight but reduced the ratio of liver weight and body weight...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723667/resistance-to-ctla-4-checkpoint-inhibition-reversed-through-selective-elimination-of-granulocytic-myeloid-cells
#20
Paul E Clavijo, Ellen C Moore, Jianhong Chen, Ruth J Davis, Jay Friedman, Young Kim, Carter Van Waes, Zhong Chen, Clint T Allen
PURPOSE: Local immunosuppression remains a critical problem that limits clinically meaningful response to checkpoint inhibition in patients with head and neck cancer. Here, we assessed the impact of MDSC elimination on responses to CTLA-4 checkpoint inhibition. EXPERIMENTAL DESIGN: Murine syngeneic carcinoma immune infiltrates were characterized by flow cytometry. Granulocytic MDSCs (gMDSCs) were depleted and T-lymphocyte antigen-specific responses were measured...
June 11, 2017: Oncotarget
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