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Cellular Immunology

Ronit Mazor, Emily King, Ira Pastan
LMB-100 is a recombinant immunotoxin being developed for cancer treatment that is composed of a Fab that binds to mesothelin and a portion of Pseudomonas exotoxin A. LMB-100 is in clinical trials for the treatment of mesothelioma and pancreatic cancer. To determine if check point modulating antibodies enhance the formation of anti-drug antibodies (ADA) against LMB-100, we treated mice with LMB-100 and four different immune modulating monoclonal antibodies that have different mechanisms of action; anti-CTLA4, anti-OX40, anti-PD-1 and anti-PDL-1...
August 28, 2018: Cellular Immunology
Chenxiao Liu, S Noushin Emami, Jean Pettersson, Lisa Ranford-Cartwright, Ingrid Faye, Ingela Parmryd
Vγ9Vδ2 T cells, the dominant γδ T cell subset in human peripheral blood, are stimulated by phosphoantigens, of which (E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate, is produced in the apicoplast of malaria parasites. Cell-free media from synchronised Plasmodium falciparum asexual ring, trophozoite, and schizont stage-cultures of high purity as well as media from ruptured schizont cultures, all stimulated Vγ9Vδ2 T cell proliferation, as did media from pure gametocyte cultures, whereas media from uninfected erythrocytes cultures did not...
August 25, 2018: Cellular Immunology
Zhixia Wang, Changming Wang, Yanni Wang, Bifan Mo, Jianghong Wei, Libing Ma, Lizong Rao, Jiying Wang, Dong Yao, Jianwei Huang, Qing Xu, Jinghuan Yang, Guangsheng Chen, Biwen Mo
It has recently been recognized that a subset of asthma patients suffer from glucocorticoid (GC) insensitivity, and glucocorticoid receptor-β (GR-β) is associated with corticosteroid resistance, but the underlying mechanisms remain unknown. Here we demonstrated that Interleukin-17A induced glucocorticoid sensitivity in human bronchial epithelial cells (16HBE) is enhanced, which is depend on E4 promoter-binding protein 4 (E4BP4) mediated GR-β expression. Our data show that the expression of E4BP4 is significantly up-regulated in 16HBE cells, and the depletion of E4BP4 dramatically decreased glucocorticoid sensitivity in IL-17A induced 16HBE cells...
August 23, 2018: Cellular Immunology
Luan Firmino-Cruz, Tadeu Diniz Ramos, Alessandra Marcia da Fonseca-Martins, Diogo Maciel-Oliveira, Gabriel Oliveira-Silva, Juliana Elena Silveira Pratti, Cecília Cavazzoni, Suzana Passos Chaves, Daniel Claudio Oliveira Gomes, Alexandre Morrot, Leonardo Freire-de-Lima, André M Vale, Celio Geraldo Freire-de-Lima, Debora Decote-Ricardo, Herbert Leonel de Matos Guedes
This work aims to study the immunomodulation of B lymphocytes during L. amazonensis infection. We demonstrated in this study that follicular B cells from draining lymph nodes of infected wild type BALB/c mice are the major source of IL-10 during infection. We infected BALB/Xid mice that developed smaller lesions in comparison with the control, but the parasite load obtained from the infected tissues was similar in both groups. We observed a reduction in the number of follicular B cells from BALB/Xid mice in relation to WT mice and, consequently, lower levels of IgM, IgG, IgG1, IgG2a and IgG2b in the serum of BALB/Xid when compared with wild type mice...
August 22, 2018: Cellular Immunology
Qun Gao, Feng Li, Shumin Wang, Zhibo Shen, Shaoyan Cheng, Yu Ping, Guohui Qin, Xinfeng Chen, Li Yang, Ling Cao, Shasha Liu, Bin Zhang, Liping Wang, Yan Sun, Yi Zhang
An important subset in regulating antitumor immunity is the maturation and accumulation of intratumor dendritic cells (DCs), inducing potent T cell cytotoxicity. In this study, we explored how the soluble abundant high-mobility group box 1 protein (HMGB1) affected DC activation and retention within lung cancers, and in which way the resultant interferon-γ (IFN-γ) further enhanced DC maturation and accumulation. It was discovered that HMGB1 was correlated with DC markers HLA-DR and CD86 in lung cancers at both mRNA and protein level...
August 20, 2018: Cellular Immunology
Juan Huang, Renyong Jia, Thomas Brunner
The nuclear receptor Small Heterodimer Partner (SHP) is a transcriptional target and inhibitor of Liver Receptor Homolog 1 (LRH-1), the transcriptional regulator of intestinal glucocorticoid (GC) synthesis. The role of SHP in the regulation of intestinal GC synthesis and its impact on T cell-mediated anti-viral immune responses in the intestinal mucosa are currently not understood. Lymphocytic choriomeningitis virus (LCMV) infection promoted intestinal GC synthesis, which was enhanced in SHP-deficient mice...
August 18, 2018: Cellular Immunology
Ivan Gudelj, Gordan Lauc, Marija Pezer
The Immunoglobulin G (IgG) glycome is well known for its heterogeneity and shows a significant degree of variation within populations. IgG glycome composition is influenced both by genes and by environment, making it an excellent biomarker of a person's general health state, i.e. biological age. IgG glycosylation appears to be highly regulated, both during homeostasis and in cases of its disturbance. Changes in IgG glycosylation patterns have been observed in aging and in various diseases. Differential IgG glycosylation is known to modulate IgG effector functions and is involved in disease development and progression, representing both a predisposition and a functional mechanism involved in disease pathology...
July 23, 2018: Cellular Immunology
Ana M Dias, Márcia S Pereira, Nuno A Padrão, Inês Alves, Ricardo Marcos-Pinto, Paula Lago, Salomé S Pinho
The diversity of glycans expression within a cell or an organism is enormous and the amount of relevant biological information that each glycan structure encodes is far from being clarified. The importance of glycans in health and life sciences is highlighted by their multiple functional implications in different cellular and molecular biology processes with impact in homeostasis and diseases, such as cancer and inflammatory conditions. Glycans actively participate in the regulatory circuits that govern both innate and adaptive immune response...
July 18, 2018: Cellular Immunology
Yasuhiko Kizuka, Sushil Mishra, Yoshiki Yamaguchi, Naoyuki Taniguchi
Glycosylation is profoundly involved in various diseases, and interactions between glycan binding proteins and their sugar ligands are plausible drug targets. Keratan sulfate (KS), a glycosaminoglycan, is downregulated in lungs by cigarette smoking, suggesting that KS is involved in smoking-related diseases, such as chronic obstructive pulmonary disease (COPD). We found that a highly sulfated KS disaccharide, L4, suppresses lung inflammation and is effective against COPD and its exacerbation in mouse models...
July 16, 2018: Cellular Immunology
Yueshui Zhao, Ling Lin, Jing Li, Zhangang Xiao, Bo Chen, Lin Wan, Mingxing Li, Xu Wu, Chi Hin Cho, Jing Shen
Over the past few decades, obesity has been recognized as low-grade chronic inflammatory disease and was contributed to systemic metabolic diseases such as type 2 diabetes (T2D). Accumulating evidence indicates that adipose tissue (AT) inflammation is a key event in the pathogenesis of obesity and obesity-associated diseases. While AT-resident immune cells play important roles in maintaining AT homeostasis, obesity changes their numbers and activities, which were accompanied by the activation of inflammatory responses...
October 2018: Cellular Immunology
Delu Che, Jue Wang, Yuanyuan Ding, Rui Liu, Jiao Cao, Yongjing Zhang, Yajing Hou, Hongli An, Zijun Gao, Tao Zhang
BACKGROUND: Mivacurium is a non-depolarizing muscle relaxant and widely used as a short-acting anesthetic. Pseudo-allergic reactions to mivacurium occur when it is administered during perioperative anesthesia. These reactions may present a serious threat to the patient's life, particularly in children. METHODS: MAS-related G protein coupled receptor-related pseudo-allergic reactions that were induced by mivacurium were investigated using skin swelling and extravasation assays in vivo and mast cell degranulation assay in vitro...
October 2018: Cellular Immunology
Junjiang Pan, Zhibing Ou, Can Cai, Peizhi Li, Jianping Gong, Xiong Z Ruan, Kun He
Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in many developed and developing countries worldwide. It has been well established that the chronic sterile inflammation caused by the NLRP3 inflammasome is closely related to NAFLD development. Kupffer cells (KCs) are involved in the pathogenesis of various liver diseases. We used methionine choline-deficient diets to establish a mouse nonalcoholic steatohepatitis (NASH) model. The expression and formation of the NLRP3 inflammasome in the KCs from the mouse and cell models were determined by Western blotting and co-immunoprecipitation...
October 2018: Cellular Immunology
Robert J Plenter, Todd J Grazia, Marilyne G Coulombe, Michelle K Nelsen, Christine M Lin, K Scott Beard, Tinalyn M Kupfer, Martin R Zamora, Ronald G Gill, Biagio A Pietra
The induction of tolerance to transplanted organs is a major objective in transplantation immunology research. Lymphocyte function-associated antigen-1 (LFA-1) interactions have been identified as a key component of the T-cell activation process that may be interrupted to lead to allograft tolerance. In mice, αLFA-1 mAb is a potent monotherapy that leads to the induction of donor-specific transferable tolerance. By interrogating important adaptive and innate immunity pathways, we demonstrate that the induction of tolerance relies on CD8+ T-cells...
October 2018: Cellular Immunology
Na-Rae Lee, Ji-Yoon Choi, Il-Hee Yoon, Jong Kil Lee, Kyung-Soo Inn
Retinoic acid-inducible gene I (RIG-I) detects viral RNAs and induces antiviral responses. During viral RNA recognition by RIG-I, tripartite motif protein 25 (TRIM25) plays a critical regulatory role by inducing K63-linked RIG-I polyubiquitination. Previous proteomics analysis revealed several phosphorylation sites on TRIM25, including tyrosine 278 (Y278), yet the roles of these modifications remain elusive. Here, we demonstrated that TRIM25 interacted with c-Src and underwent tyrosine phosphorylation by c-Src kinase upon viral infection and the phosphorylation is required for the complete activation of RIG-I signaling...
October 2018: Cellular Immunology
Juan Zhang, Jing-Yi Ma, Qiu-Hong Li, Hui Su, Xin Sun
Great interest has been taken in the use of beneficial bacteria for allergic diseases recently, but the underlying mechanisms through which probiotics induces immune regulation or immune tolerance are poorly understood. We aimed to explore whether Lactobacillus rhamnosus GG (LGG)-induced beneficial effect relates to the change of microbiota. LGG was administered orally to mouse model of ovalbumin (OVA)-induced allergic airway inflammation. Our findings manifested that LGG-treatment contributes to protect against OVA-induced allergic airway inflammation by expanding mesenteric CD103+ DCs and accumulating mucosal Tregs...
October 2018: Cellular Immunology
Rossana Domenis, David Pilutti, Maria Orsaria, Stefania Marzinotto, Veronica Candotti, Giulia Bosisio, Michela Bulfoni, Maria Elisabetta Ruaro, Carla Di Loreto, Vincenzo Della Mea, Eleonora Toffoletti, Ambrogio P Londero, Laura Mariuzzi, Giorgia Gri
S100A4 protein is expressed in fibroblasts during tissue remodelling and in cancer stem cells and it induces the metastatic spread of tumor cells. In mast cells (MCs) S100A4 have been found in some pathological conditions, but its function in normal MCs remains to be described. The purpose of this study was to characterize the cellular localization of the S100A4 protein in MCs of human tissues with inflammatory or tumor disorders and, to determine the consequence of reducing its expression in MC response. We found that tissue resident MCs stained positive to S100A4...
October 2018: Cellular Immunology
E Vermeersch, S Liénart, A Collignon, S Lucas, A Gallimore, C Gysemans, D Unutmaz, K Vanhoorelbeke, S F De Meyer, W Maes, H Deckmyn
GARP is a transmembrane protein that presents latent TGF-β1 on the surface of regulatory T cells (Tregs). Neutralizing anti-GARP monoclonal antibodies that prevent the release of active TGF-β1, inhibit the immunosuppressive activity of human Tregs in vivo. In this study, we investigated the contribution of GARP on mouse Tregs to immunosuppression in experimental tumors. Unexpectedly, Foxp3 conditional garp knockout (KO) mice challenged orthotopically with GL261 tumor cells or subcutaneously with MC38 colon carcinoma cells did not show prolonged survival or delayed tumor growth...
October 2018: Cellular Immunology
Megan A Forrester, Heather J Wassall, Lindsay S Hall, Huan Cao, Heather M Wilson, Robert N Barker, Mark A Vickers
Macrophages are key in orchestrating immune responses to micro-environmental stimuli, sensed by a complex set of surface receptors. The human cell line THP-1 has a monocytic phenotype, including the ability to differentiate into macrophages, providing a tractable, standardised surrogate for human monocyte-derived macrophages. Here we assessed the expression of 49 surface markers including Fc, complement, C-type lectin and scavenger receptors; TIMs; Siglecs; and co-stimulatory molecules by flow cytometry on both THP-1 monocytes and macrophages and following macrophage activation with seven standard conditioning/polarizing stimuli...
October 2018: Cellular Immunology
Samira Elikaee, Mehdi Mohebali, Sassan Rezaei, Hamid Eslami, Ali Khamesipour, Hossein Keshavarz, Mohammad Reza Eshraghian
Genetically modifying Leishmania major by eliminating essential virulence genes have been proposed as potential vaccine candidates. p27 is a COX component that is responsible for ATP synthesis. In this study a new mutant of Leishmania major (L. major) (MRHO/IR/75/ER) lacking the p27 gene (Lmp27- / - ) was produced via homologous recombination, marking the first time such a strain has been developed. In vitro macrophage infectivity and In vivo safety, and overall immunogenicity were evaluated at various time periods following inoculation into BALB/c mice...
October 2018: Cellular Immunology
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