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Cellular Immunology

Andrew O Yam, Tatyana Chtanova
Neutrophils are the first cellular responders of the immune system. They employ their impressive arsenal of microbicidal molecules to provide rapid and efficient defense against pathogens. However, the role of neutrophils extends far beyond microbial destruction to include tissue repair and remodeling, provision of signals to the adaptive immune system and body homeostasis. Intravital imaging has allowed the visualization of neutrophils in their native environment in both health and disease and provided crucial insights into their mechanisms of action...
January 23, 2019: Cellular Immunology
A Laskewitz, K L van Benthem, T E C Kieffer, M M Faas, R N Verkaik-Schakel, T Plösch, S A Scherjon, J R Prins
Obesity is seen as a low grade inflammatory state, and is associated with adverse pregnancy outcomes. Disturbed macrophage characteristics might be essential in obesity associated pregnancy pathology via effects on the regulation of angiogenesis and placental development. This study aims to address the effects of maternal obesity on macrophage subsets in the decidua of women with term uncomplicated pregnancies. Macrophages were isolated from the decidua basalis and decidua parietalis of women with pre-gravid BMI < 25 (control) and BMI > 30 (obese)...
January 11, 2019: Cellular Immunology
Anwei Chen, Di Yang, Xingtian Xuan, Heather Miller, Xiaoyan Luo, Jie Yu, Gangyi Yang, Hua Wang, Chaohong Liu
As an atypical guanine nucleotide exchange factor (GEF), Dock5 has been extensively studied in cellular functions. However, the role of Dock5 on B-cell immunity still remain elusive. In this study, we generated a Dock5 knockout mouse model to study the effect of Dock5 deficiency on B cell development, differentiation and BCR signaling. We found that the absence of Dock5 leads to a moderate effect on B cell development in the bone marrow and reduces follicular (FO) and marginal zone (MZ) B cells. Mechanistically, the key positive upstream B-cell receptor (BCR) signaling molecules, CD19 and Brutons tyrosine kinase (Btk), whose activation determines the fate of FO and MZ B cells, is reduced in Dock5 KO B cells upon antigenic stimulation by using total internal reflection fluorscence microscopy (TIRF) and immunoblot...
January 11, 2019: Cellular Immunology
Runan Zhang, Yanyue Zhang, Jianhua Hu, Wei Wu, Xiaoming Chen, Zhongjie Lu, Rong Yang, Yaping Huang, Jun Fan
Human cytomegalovirus (HCMV) infection is a leading cause of morbidity and mortality in immunocompromised patients, but no specific therapeutic strategy is effective clinically, despite recent achievements. HCMV-specific T-cell therapy was thought to be helpful for the management of HCMV infection. To conduct a deep exploration, we investigated the possibility of engineering peripheral blood mononuclear cells (PBMCs) from immunocompetent and immunocompromised subjects with specific T-cell receptor (TCR) genes...
January 2, 2019: Cellular Immunology
Young K Hong, Yan Li, Harshul Pandit, SuPing Li, Zachary Pulliam, Qianqian Zheng, Youxi Yu, Robert C G Martin
BACKGROUND: Anti-PDL-1 immunotherapy for Hepatocellular Carcinoma (HCC) demonstrated a mixed response. Polycomb Repressor Complex 2(PRC2) contributes to the initiation and progression of HCC by suppressing tumor antigens and inhibiting an immune response. Two components of epigenetic modulation are Enhancer of Zeste Homolog 2 (EZH2, the catalytic component of PRC2) and DNA Methyltransferase 1 (DNMT1). We aim to investigate the potential role of epigenetic therapy targeting EZH2 and DNMT1 as a novel strategy to modulate immunotherapy response in HCC...
January 2, 2019: Cellular Immunology
Ivana Vujnović, Ivan Pilipović, Nebojša Jasnić, Raisa Petrović, Veljko Blagojević, Nevena Arsenović-Ranin, Zorica Stojić-Vukanić, Jelena Djordjević, Gordana Leposavić
Males exhibit stronger sympathetic nervous system (SNS) activity, but weaker primary CD4+ T-cell (auto)immune responses. To test the role of catecholamines, major end-point SNS mediators, in this dimorphism, influence of propranolol (β-adrenoceptor blocker) on mitogen/neuroantigen-stimulated CD4+ T cells from female and male EAE rat draining lymph node (dLN) cell cultures was examined. Male rat dLNs exhibited higher noradrenaline concentration and frequency of β2 -adrenoceptor-expressing CD4+ T lymphocytes and antigen presenting cells...
December 26, 2018: Cellular Immunology
Faji Yang, Yang Liu, Haozhen Ren, Guang Zhou, Xianwen Yuan, Xiaolei Shi
During the process of NAFLD progression, ER-stress is activated in macrophages and induces the pro-inflammatory polarization of macrophage. As one of the three ER membrane resident proteins, pancreatic eIF-2alpha kinase (PERK) plays an important role in ER stress, but its participation in macrophage polarization is largely unknown. In this study, we found that the PA mediated ER-stress activation could induce M1-type polarization in macrophages, and this phenotype polarization could be inhibited by ER-stress inhibitor 4-PBA as well as GSK2656157, an inhibitor of PERK...
December 21, 2018: Cellular Immunology
Yu Ping, Mengjia Song, Meng Wang, Zhiqin Li, Yi Zhang
T cell receptors (TCR) diversity is known to serve as a defining hallmark of the antigen-reactive T cell repertoire. Complementarity determining region 3 (CDR3) was the most important region for the recognition of peptide-major histocompatibility complex (MHC) complexes and represented the diversity of TCR repertoire. In this study, we detected the CDR3 spectratypes by complexity scoring system to assess TCR repertoire diversity and further analyzed the correlation of CDR3 score with CD8+ T cell function and with the prognosis of chronic hepatitis C virus (HCV)-infected patients...
December 20, 2018: Cellular Immunology
Jason R Lees
Autoimmune diseases are heterogeneous group of disorders that together represent an enormous societal and medical problem. CD4+ T cells have critical roles in the initiation and pathogenesis of autoimmune disease. As such, modulation of T cell activity has proven to have significant therapeutic effects in multiple autoimmune settings. T cell activation is a complex process with multiple potential therapeutic targets, many of which have been successfully utilized to treat human disease. Current pharmacological treatment largely targets T cell intrinsic activities as a means of treating various autoimmune disorders...
December 11, 2018: Cellular Immunology
David Langan, Eugene Y Kim, Kamal D Moudgil
Observations in patients with autoimmune diseases and studies in animal models of autoimmunity have revealed that external environmental factors including exposure to microbes and the state of the host gut microbiota can influence susceptibility to autoimmunity and subsequent disease development. Mechanisms underlying these outcomes continue to be elucidated. These include deviation of the cytokine response and imbalance between pathogenic versus regulatory T cell subsets. Furthermore, specific commensal organisms are associated with enhanced severity of arthritis in susceptible individuals, while exposure to certain microbes or helminths can afford protection against this disease...
December 10, 2018: Cellular Immunology
S M Lunin, M O Khrenov, O V Glushkova, S B Parfenyuk, T V Novoselova, E G Novoselova
Characteristics of the mouse model of relapsing-remitting experimental autoimmune encephalomyelitis (rEAE) closely resemble manifestations of multiple sclerosis in humans. In the present study, we investigated the mechanisms of inflammatory response, focusing on NF-κB pathway activation. Cytokine response in rEAE mice was multiphasic: the early phase was characterized by the increase in interferon-γ level in plasma. In the later stage, the level of interleukin-17, but not of interferon-γ, was increased. The early phase of rEAE was also accompanied by increased RelA/p65 phosphorylation at Ser276 in spleen cells, whereas the rEAE maintenance phase was characterized by RelA/p65 phosphorylation at Ser536 and IKK phosphorylation...
December 8, 2018: Cellular Immunology
Myun Soo Kim, Sora Lee, Su-Jin Jung, Sunyoung Park, Kyung Eun Kim, Tae Sung Kim, Hyun Jeong Park, Daeho Cho
Erythroid differentiation regulator 1 (Erdr1) has been identified as a stromal survival factor released under stressful conditions. Previously, Erdr1 was reported to be expressed highly in thymus, but roles of Erdr1 in thymus were not known. Here, the effects of Erdr1 on T cell development were investigated. The expression of Erdr1 was higher in thymus than bone marrow and Erdr1 was detected in both the cortex and medulla of thymus. Erdr1 treatment significantly induced the expression of activation marker, CD69, from thymocytes in the presence of TCR stimuli in vitro and the induction was dependent on increased Ca2+ influx...
December 5, 2018: Cellular Immunology
N J Geraghty, D Watson, R Sluyter
Allogeneic haematopoietic stem cell transplantation (HSCT) is a frequent curative therapy for numerous haematological malignancies. However, HSCT is limited by the occurrence of graft-versus-host disease (GVHD), with current therapies restricted to general immunosuppression. Activation of the P2X7 receptor by extracellular adenosine triphosphate (ATP) causes inflammation and tissue damage in GVHD. Short-term pharmacological blockade of P2X7 has been shown to reduce clinical disease and/or reduce inflammatory markers in allogeneic and humanized mouse models of GVHD...
December 4, 2018: Cellular Immunology
Juan Villar-Vesga, Camilo Grajales, Catalina Burbano, Adriana Vanegas-García, Carlos H Muñoz-Vahos, Gloria Vásquez, Mauricio Rojas, Diana Castaño
Patients with rheumatoid arthritis (RA) have increased amount of platelet-derived microparticles (PMPs) positive for citrullinated peptides (CPs) that form immune complexes (PMPs-ICs). Monocytes are important inflammatory mediators that play a role in the clearance of PMPs-ICs. We aimed to generate PMPs-ICs in vitro and determine its effect on monocytes from patients with RA and healthy individuals (HI). PMPs from patients showed platelet markers, mitochondria content, and phosphatidylserine exposure similar to PMPs from HI...
December 4, 2018: Cellular Immunology
John Reiser, Kavitha Sadashivaiah, Aki Furusawa, Arnob Banerjee, Nevil Singh
CD8+ T cell differentiation is controlled by the transcription factors T-bet and Eomesodermin, in concert with the cytokines IL-2, IL-10 and IL-12. Among these pathways, the mechanisms by which T-box proteins and IL-10 interact to promote a memory T cell fate remain poorly understood. Here, we show that Eomes and IL-10 drive a central memory phenotype in murine CD8+ T cells. Eomes expression led to increased IL-10 expression by the effector CD8+ T cells themselves as well as an increase in the level of the lymph node homing selectin CD62L...
December 1, 2018: Cellular Immunology
Shaopeng Zhang, Qihang Wu, Hang Lei, Hui Zheng, Fang Zhou, Zhanqiang Sun, Junwei Zhao, Xiaoli Yu, Shulin Zhang
Lipoarabinomannan (LAM) is an important virulent factor secreted by mycobacteria, which generally elicit a strong immune response in the host. In this study, the structural difference of LAMs from three mycobacterial strains, Mycobacterium tuberculosis H37Rv, Mycobacterium smegmatis mc2 155 and a newly discovered clinical isolate, M. sp. QGD101, was analyzed and further evaluated whether these LAMs can induce DC maturation and promote the immunomodulatory properties. The results reveal that the major structural difference of these LAMs is the amount of mannosyl residues, especially at the terminal end of LAM, which play a key role in determining the divergent response of DCs after mycobacterial infection...
November 30, 2018: Cellular Immunology
Mariele Guerra, Tania Luna, Anselmo Souza, Camila Amorim, Natália B Carvalho, Lucas Carvalho, Davi Tanajura, Luciana S Cardoso, Edgar M Carvalho, Silvane Santos
BACKGROUND: HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) is related with high proviral load, high proinflammatory cytokine levels, and passage of infected cell from the blood to the central nervous system. We aimed to evaluate the participation of chemokines and adhesion molecules in HAM/TSP pathogenesis. METHODS: CXCL9, CXCL10, sICAM-1, and sVCAM-1 were determined by ELISA in serum and cerebrospinal fluid (CSF) of HTLV-1 infected individuals...
December 2018: Cellular Immunology
Jie Shao, Qiuping Xu, Shu Su, Jia Wei, Fanyan Meng, Fangjun Chen, Yang Zhao, Juan Du, Zhengyun Zou, Xiaoping Qian, Baorui Liu
Adoptive immunotherapy is a promising cancer treatment that entails infusion of immune cells manipulated to have antitumor specificity, in vitro. Antigen-specific cytotoxic T lymphocytes are the main executors of transformed cells during cancer immunotherapy. To induce antigen-specific cytotoxic T lymphocytes, we developed artificial antigen-presenting cells (aAPCs) by engineering K562 cells with electroporation to direct the stable expression of HLA-A∗0201, CD80, and 4-1BBL. Our findings demonstrate that after three stimulation cycles, the aAPCs promoted the induction of antigen-specific cytotoxic T lymphocytes with a less differentiated "young" phenotype, which enhanced immune responses with superior cytotoxicity...
December 2018: Cellular Immunology
Barry Paul, Shuqi Kang, Zhihong Zheng, Yubin Kang
Despite significant improvements in the overall survival of patients with multiple myeloma (MM) over the past 15 years, the disease remains incurable. Treatment options are limited for patients who have relapsed or are refractory to immunomodulatory drugs (IMiDs), proteasome inhibitors, and monoclonal antibodies. In these patients, immunotherapies such as checkpoint inhibitors, oncolytic vaccines, and chimeric antigen receptor (CAR) T cells provide a potentially effective alternative treatment. While checkpoint inhibitors are effective in prolonging overall survival in some patients with advanced solid cancers and Hodgkin lymphoma, they have not demonstrated significant activity as a single agent in MM...
December 2018: Cellular Immunology
Saima Naz, Rafiq Ahmad Khan, Jeevan Giddaluru, Srikanth Battu, Sandeep Kumar Vishwakarma, Mabu Subahan, Vishnupriya Satti, Nooruddin Khan, Aleem Ahmed Khan
Ulcerative colitis (UC) is a persistent inflammatory illness, which is clinically categorised as Inflammatory bowel disease (IBD), affecting millions of people worldwide. The precise cause behind the pathology of the disease remains unknown. However, the involvement of multiple factors including genetic predisposition, immunological deregulations, microbiota imbalance, and environmental triggers has been suggested. Amongst all these factors, the over-active immunological response reported in UC patients seems to be a promising target for therapy...
December 2018: Cellular Immunology
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