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Immune modulation

Jessica C Stark, Euan Wallace, Rebecca Lim, Bryan Leaw
Microglia, the resident immune cells in the brain, are the first responders to inflammation or injury in the central nervous system. Recent research has revealed microglia to be dynamic, capable of assuming both pro-inflammatory and anti-inflammatory phenotypes. Both M1 (pro-inflammatory) and M2 (pro-reparative) phenotypes play an important role in neuroinflammatory conditions such as perinatal brain injury, and exhibit differing functions in response to certain environmental stimuli. The modulation of microglial activation has been noted to confer neuroprotection thus suggesting microglia may have therapeutic potential in brain injury...
February 16, 2018: Journal of Visualized Experiments: JoVE
Peter D Koch, Howard R Miller, Gary Yu, John A Tallarico, Peter K Sorger, Yuan Wang, Yan Feng, Jason R Thomas, Nathan T Ross, Timothy Mitchison
We screened a library of bioactive small molecules for activators and inhibitors of innate immune signaling through IRF3 and NFkB pathways with the goals of advancing pathway understanding and discovering probes for immunology research. We used high content screening to measure the translocation from the cytoplasm to nucleus of IRF3 and NFkB in primary human macrophages; these transcription factors play a critical role in the activation of STING and other pro-inflammatory pathways. Our pathway activator screen yielded a diverse set of hits that promoted nuclear translocation of IRF3 and/or NFkB, but the majority of these compounds did not cause activation of downstream pathways...
March 19, 2018: ACS Chemical Biology
Kirstin Harling, Ernest Adankwah, Alptekin Güler, Anthony Afum-Adjei Awuah, Louis Adu-Amoah, Ertan Mayatepek, Ellis Owusu-Dabo, Norman Nausch, Marc Jacobsen
T-cells critically contribute to protection against Mycobacterium tuberculosis infection, and impaired T-cell responses can lead to disease progression. Pro-inflammatory and immunosuppressive cytokines affect T-cells, and fine-tuned regulation of cytokine signaling via the Jak/STAT signaling pathways is crucial for appropriate T-cell function. Constitutive STAT3 phosphorylation as a consequence of aberrant cytokine signaling has been described to occur in pathognomonic T-cell responses in inflammatory and autoimmune diseases...
March 19, 2018: Cellular & Molecular Immunology
Riccardo Calvani, Anna Picca, Maria Rita Lo Monaco, Francesco Landi, Roberto Bernabei, Emanuele Marzetti
In recent years, an extensive body of literature focused on the gut-brain axis and the possible role played by the gut microbiota in modulating brain morphology and function from birth to old age. Gut microbiota has been proposed as a relevant player during the early phases of neurodevelopment, with possible long-standing effects in later life. The reduction in gut microbiota diversity has also become one of the hallmarks of aging, and disturbances in its composition are associated with several (age-related) neurological conditions, including depression, Alzheimer's disease, and Parkinson's disease...
2018: Frontiers in Medicine
Periklis G Foukas, Sotirios Tsiodras, Panagiota Economopoulou, Aris Spathis, Maria Mademli, Konstantinos Leventakos, Amanda Psyrri, Petros Karakitsos, Ioannis G Panayiotides
The development of immune system modulating agents, such as immune checkpoint inhibitors (ICIs), has revolutionized cancer treatment. Nivolumab, a human monoclonal antibody against PD-1, has emerged as an efficient treatment for various malignancies, including non-small cell lung cancer (NSCLC); however, it is associated with important immune related side-effects, attributed to organ-specific inflammation, such as immune-mediated pneumonitis, a relatively uncommon, albeit potentially fatal adverse event. We herein present the unique case of severe interstitial pneumonitis with concomitant detection of Human Herpes Virus 6 (HHV-6) in a nivolumab treated patient with NSCLC...
2018: IDCases
Riccardo Marconcini, Francesco Spagnolo, Luigia Stefania Stucci, Simone Ribero, Elena Marra, Francesco De Rosa, Virginia Picasso, Lorenza Di Guardo, Carolina Cimminiello, Stefano Cavalieri, Laura Orgiano, Enrica Tanda, Laura Spano, Alfredo Falcone, Paola Queirolo
Metastatic melanoma was the first malignancy in which immune checkpoint inhibitors demonstrated their successful efficacy. Currently, the knowledge on the interaction between the immune system and malignant disease is steadily increasing and new drugs and therapeutic strategies are overlooking in the clinical scenario. To provide a comprehensive overview of immune modulating drugs currently available in the treatment of melanoma as well as to discuss of possible future strategies in the metastatic melanoma setting, the present review aims at analyzing controversial aspects about the optimal immunomodulating treatment sequences, the search for biomarkers of efficacy of immunocheckpoint inhibitors, and innovative combinations of drugs currently under investigation...
February 23, 2018: Oncotarget
Jun Li, Qian Li, Ling Chen, Yanli Gao, Bei Zhou, Jingyun Li
Infantile hemangioma (IH) is the most common vascular tumour in infants. The pathogenesis of IH is complex and poorly understood. Therefore, achieving a deeper understanding of IH pathogenesis is of great importance. Here, we used the Ribo-Zero RNA-Seq and HiSeq methods to examine the global expression profiles of protein-coding transcripts and non-coding RNAs, including miRNAs and lncRNAs, in IH and matched normal skin controls. Bioinformatics assessments including gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) pathway analyses were performed...
February 23, 2018: Oncotarget
You-Take Oh, Guoqing Qian, Jiusheng Deng, Shi-Yong Sun
Monocyte chemotactic protein-induced protein-1 (MCPIP1; also called Regnase-1) encoded by the ZC3H12A gene critically regulates inflammatory responses and immune homeostasis primarily by RNase-dependent and -independent mechanisms. However, the relationship of MCPIP1 with apoptosis and cancer and the underlying mechanisms are largely unclear. The current study has demonstrated a previously uncovered connection between MCPIP1 and the negative regulation of death receptor 5 (DR5; also known as TRAIL-R2 or killer/DR5), a cell surface receptor for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which is produced endogenously by various immune cells such as T cells...
March 19, 2018: Oncogene
Silvana Konermann, Peter Lotfy, Nicholas J Brideau, Jennifer Oki, Maxim N Shokhirev, Patrick D Hsu
Class 2 CRISPR-Cas systems endow microbes with diverse mechanisms for adaptive immunity. Here, we analyzed prokaryotic genome and metagenome sequences to identify an uncharacterized family of RNA-guided, RNA-targeting CRISPR systems that we classify as type VI-D. Biochemical characterization and protein engineering of seven distinct orthologs generated a ribonuclease effector derived from Ruminococcus flavefaciens XPD3002 (CasRx) with robust activity in human cells. CasRx-mediated knockdown exhibits high efficiency and specificity relative to RNA interference across diverse endogenous transcripts...
March 8, 2018: Cell
Yolanda Revilla, Daniel Pérez-Núñez, Juergen A Richt
African swine fever (ASF) is an acute and often fatal disease affecting domestic pigs and wild boar, with severe economic consequences for affected countries. ASF is endemic in sub-Saharan Africa and the island of Sardinia, Italy. Since 2007, the virus emerged in the republic of Georgia, and since then spread throughout the Caucasus region and Russia. Outbreaks have also been reported in Belarus, Ukraine, Lithuania, Latvia, Estonia, Romania, Moldova, Czech Republic, and Poland, threatening neighboring West European countries...
2018: Advances in Virus Research
Tian Liu, Dongliang Zhang, Yuan Zhang, Xiangsheng Xu, Bo Zhou, Liang Fang, Yun Zhang, Yingjun Su, Boquan Jin, Ran Zhuang, Shuzhong Guo
BACKGROUND/AIMS: Regulatory T cells (Tregs) play key roles in maintaining peripheral tolerance and preventing autoimmune disease. Treg modulation could be helpful in treating malignancies, autoimmune disease, and allergies, as well as to facilitate organ transplantation. Signals transduced by co-stimulatory molecules are essential for Treg differentiation, homeostasis, and function. One well-known active receptor, CD226, also known as DNAM-1 or PTA1, is an adhesion molecule that interacts primarily with CD155 and is involved in Treg differentiation and immune tolerance to transplanted tissue...
March 13, 2018: Cellular Physiology and Biochemistry
Erika Contreras-Nuñez, Gerardo Blancas-Flores, Miguel Cruz, Julio Cesar Almanza-Perez, Jaime H Gomez-Zamudio, Jose Luis Ventura-Gallegosc, Alejandro Zentella-Dehesa, Roberto-Lazzarini, Ruben Roman-Ramos, Francisco Javier Alarcon-Aguilar
Glycine modulates inflammatory processes mediated by macrophages and adipocytes through decreasing the secretion of TNF-α, IL-6, and leptin, while increasing adiponectin. These effects have been associated with the inactivation of NF-κB in response to TNF-α, across an increase of its inhibitor IκB-α in adipocytes. However, glycine upstream mainly influences the IκB kinase (IKK) complex, a multi-protein kinase complex considered a critical point in regulation of the NF-κB pathway; whether that is responsible for the TNF-α-induced phosphorylation of IkB has not been explored...
March 15, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Nadia A Al-Banna, Farhan Cyprian, M John Albert
Campylobacter jejuni is an important enteric pathogen that causes diarrheas of different degrees of severity and several extra-intestinal manifestations, including Guillain-Barre syndrome. The variability of disease outcomes is thought to be linked to the immune response induced by C. jejuni. The virulence factors of C. jejuni induce a pro-inflammatory response, that is initiated by the intestinal epithelial cells, propagated by innate immune cells and modulated by the cells of the adaptive immune response...
March 10, 2018: Cytokine & Growth Factor Reviews
Cristian Alfredo Segura-Cerda, Michel de Jesús Aceves-Sánchez, Brenda Marquina-Castillo, Dulce Mata-Espinoza, Jorge Barrios-Payán, Perla Jazmín Vega-Domínguez, César Pedroza-Roldán, Jorge Bravo-Madrigal, Alba Adriana Vallejo-Cardona, Rogelio Hernández-Pando, Mario Alberto Flores-Valdez
Pellicles, a type of biofilm, have gathered a renewed interest in the field of tuberculosis as a structure that mimics some characteristics occurring during M. tuberculosis infection, such as antibiotic recalcitrance and chronicity of infection, and as a source of antigens for humoral response in infected guinea pigs. In other bacteria, it has been well documented that the second messenger c-di-GMP modulates the transition from planktonic cells to biofilm formation. In this work, we used the live vaccine Mycobacterium bovis BCG to determine whether deletion of genes involved in c-di-GMP metabolism would affect interaction with macrophages, capacity to induce immune response in a murine cell line and mice, and how the protein profile was modified when grown as surface pellicles...
March 14, 2018: Vaccine
Qiang Cai, Baoye He, Karl-Heinz Kogel, Hailing Jin
In plants, small RNA (sRNA)-mediated RNA interference (RNAi) is critical for regulating host immunity against bacteria, fungi, oomycetes, viruses, and pests. Similarly, sRNAs from pathogens and pests also play an important role in modulating their virulence. Strikingly, recent evidence supports that some sRNAs can travel between interacting organisms and induce gene silencing in the counter party, a mechanism termed cross-kingdom RNAi. Exploiting this new knowledge, host-induced gene silencing (HIGS) by transgenic expression of pathogen gene-targeting double-stranded (ds)RNA has the potential to become an important disease-control method...
March 14, 2018: Current Opinion in Microbiology
Jiangyan Xia, Zhen Lu, Shanwu Feng, Jianjun Yang, Muhuo Ji
Stressful life events are thought to be triggering factors of numerous neuropsychiatric disorders, including anxiety and depression. However, the interactions between chronic unpredictable mild stress (CUMS) and immune stimulation have not been thoroughly investigated. In the present study, we evaluated the effects of lipopolysaccharide (LPS) challenge at different time points on CUMS-induced anxiety- and depression-like behaviors. At 1 day before, 18 or 35 days following the initial of CUMS, mice were intraperitoneally given a single LPS (0...
March 14, 2018: International Immunopharmacology
Małgorzata Tomczyńska, Joanna Saluk-Bijak
Autoimmune thyroid diseases include several distinct clinical entities, mainly Graves' disease and Hashimoto's thyroiditis. An incompetent immune response directed against the body's own tissues, and the production of antibodies against specific cell antigens accompanied by chronic inflammation, all occur in autoimmune thyroid diseases. The autoimmune process is induced by genetic and environmental factors that are difficult to identify and generates the development of concomitant diseases in other systems...
March 15, 2018: Acta Biochimica Polonica
Hanwen Tian, Junming Miao, Fumei Zhang, Feng Xiong, Feimei Zhu, Jinyu Li, Xiaoying Wang, Shanzhe Chen, Junli Chen, Ning Huang, Yi Wang
The urinary tract is vulnerable to frequent challenges from environmental microflora. Uropathogenic Escherichia coli (UPEC) makes a major contribution to urinary tract infection (UTI). Previous studies have characterized positive roles of non-histone nuclear protein HMGN2 in lung epithelial innate immune response. In the study presented here, we found HMGN2 expression was up-regulated in UPEC J96-infected urothelium. Surprisingly, over-expression of HMGN2 promoted disruption of BECs 5637 cells' intercellular junctions by down-regulating tight junction (TJs) components' expression and physical structure under J96 infection...
March 17, 2018: Acta Biochimica Polonica
Peng Xia, Xiaoting Gong, Lin Xiao, Yida Wang, Tianzhuo Zhang, Qingyuan Liao, Xiaoning Mo, Xiaoyan Qiu, Jing Huang
CCDC134 (coiled-coil domain containing 134), a cytokine-like molecule, was previously reported to have antitumor effects via by augmenting CD8+ T-cell-mediated immunity. However, the dynamic change of CCDC134 expression pattern in spinal cords that may be involved in the progression of experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, remains unclear. In this study, we found that CCDC134 were markedly increased in the spinal cord during the progression of EAE. Furthermore, we demonstrated that CCDC134 significantly reduced the severity of EAE and slowed down the ongoing EAE, which correlated with reduced spinal cord inflammation and demyelination...
March 13, 2018: Brain, Behavior, and Immunity
Fabio L M Ricciardolo, Gert Folkerts, Anna Folino, Barbara Mognetti
Bradykinin, a pro-inflammatory molecule, and its related peptides have been studied for their effects on acute reactions in upper and lower airways, where they can be synthesised and metabolized after exposure to different stimuli including allergens and viral infection. Bradykinin B1 and B2 receptors are constitutively expressed in the airways on several residential and/or immune cells. Their expression can also be induced by inflammatory mediators, usually associated with eosinophil and neutrophil recruitment, such as IL-4, IL-13, TNF-α, IL-6 and IL-8, via intracellular MAPK and NF-κB signalling...
March 13, 2018: European Journal of Pharmacology
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