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Immunology and Cell Biology

Lisa Worley, Stuart G Tangye, Cindy S Ma
Interleukin-9 (IL-9) producing CD4+ Th9 cells are a unique subset of effector cells involved in both health and disease. Th9 cells have been associated with protective immunity during parasitic infections with helminths, protozoans and extracellular pathogens, but implicated in disease states such as allergic asthma, atopic dermatitis, food allergy and autoimmune conditions including multiple sclerosis and ulcerative colitis. Here, we review the cytokine signalling pathways and downstream transcription factors required for IL-9 expression and how human primary immunodeficiencies due to monogenic mutations can help elucidate the complex requirements for human Th9 cell differentiation...
October 25, 2018: Immunology and Cell Biology
Shuang Cao, Guohua Wang, Jia Wang, Cheng Li, Le Zhang
In this study, we sought to predict the effects of a certain circular RNA (circRNA), hsa_circ_101280 (also known as hsa_circ_0100929 and hsa_circ_SLAIN1), on hepatocellular carcinoma (HCC) cells and to determine the potential mechanism. After screening differentially expressed circRNAs in HCC tissues through GEO data analysis, hsa_circ_101280 was found to be highly expressed, and its high expression was verified in HCC cell lines with qRT-PCR along with the low expression of its downstream miRNA miR-375. Colony formation and flow cytometry assays showed that both hsa_circ_101280 silencing and miR-375 overexpression restrained proliferation and promoted apoptosis in HCC cells...
October 9, 2018: Immunology and Cell Biology
Ehab A Ayaub, Karun Tandon, Manreet Padwal, Jewel Imani, Hemisha Patel, Anisha Dubey, Olivia Mekhael, Chandak Upagupta, Anmar Ayoub, Anna Dvorkin-Gheva, James Murphy, Philipp S Kolb, Sarka Lhotak, Jeffrey G Dickhout, Rick C Austin, Martin Rj Kolb, Carl D Richards, Kjetil Ask
Although recent evidence has shown that IL-6 is involved in enhanced alternative activation of macrophages toward a pro-fibrotic phenotype, the mechanisms leading to their increased secretory capacity are not fully understood. Here, we investigated the effect of IL-6 on endoplasmic reticulum (ER) expansion and alternative activation of macrophages in vitro. An essential mediator in this ER expansion process is the IRE1 pathway, which possesses a kinase and endoribonuclease domain to cleave XBP1 into a spliced bioactive molecule...
October 9, 2018: Immunology and Cell Biology
Samantha J Winter, Heike Kunze-Schumacher, Esther Imelmann, Zoe Grewers, Tabea Osthues, Andreas Krueger
Mucosal-associated invariant T cells (MAIT cells) constitute a major fraction of innate-like T cells in humans with critical roles in defense against microbial pathogens and in maintaining mucosal integrity. However, the molecular mechanisms underlying MAIT cell development remain largely elusive. Here we investigated the role of miR-181a/b-1, a pair of microRNAs that serve as rheostat of TCR signal strength, in this process. Loss of miR-181a/b-1 in mice resulted in a profound arrest in early MAIT cell development...
October 6, 2018: Immunology and Cell Biology
Jérémie Rosain, Xiao-Fei Kong, Ruben Martinez-Barricarte, Carmen Oleaga-Quintas, Noé Ramirez-Alejo, Janet Markle, Satoshi Okada, Stéphanie Boisson-Dupuis, Jean-Laurent Casanova, Jacinta Bustamante
Mendelian susceptibility to mycobacterial disease (MSMD) is caused by inborn errors of IFN-γ immunity. Since 1996, disease-causing mutations have been found in 11 genes, which, through allelic heterogeneity, underlie 21 different genetic disorders. We briefly review here progress in the study of molecular, cellular and clinical aspects of MSMD since the last comprehensive review published in 2014. Highlights include the discoveries of (1) a new genetic etiology, autosomal recessive signal peptide peptidase-like 2 A deficiency, (2) TYK2-deficient patients with a clinical phenotype of MSMD, (3) an allelic form of partial recessive IFN-γR2 deficiency, and (4) two forms of syndromic MSMD: RORγ/RORγT and JAK1 deficiencies...
September 28, 2018: Immunology and Cell Biology
Taha Al-Shaikhly, Hans D Ochs
Hyper IgE syndromes comprise a group of rare primary immunodeficiency disorders characterized by a triad of atopic dermatitis, recurrent skin and lung infections along with elevated IgE levels. Job syndrome or autosomal dominant hyper IgE syndrome due to heterozygous loss-of-function mutations with dominant negative effect in STAT3 is the prototype of these disorders. However, several other genetically characterized immunodeficiency disorders have been identified over the past decade and joined the umbrella of hyper IgE syndromes including, autosomal recessive mutations in the DOCK8, ZNF431, and PGM3 genes and heterozygous mutations with dominant negative effect in the CARD11 gene...
September 28, 2018: Immunology and Cell Biology
Birgit Zimmermann-Geller, Sina Köppert, Nina Kesel, Rebecca Hasseli, Sebastian Ullrich, Stephanie Lefèvre, Klaus Frommer, Thorsten Gehrke, Markus Schönburg, Stephan Rehart, Udo Schumacher, Ulf Müller-Ladner, Elena Neumann
Leukocytes travel within the circulation and enter connective tissues by interactions with endothelium of postcapillary venules mediated by cell adhesion molecules, summarized as the leukocyte adhesion cascade. In the severe combined immunodeficient (SCID) mouse model, rheumatoid arthritis (RA) synovial fibroblasts (SF) migrated to distant cartilage through the vasculature. Therefore, RASF adhesion toward endothelial cells (EC) and E- and P-selectins were analyzed. Cell-to-cell binding assays between SF and EC were performed...
September 25, 2018: Immunology and Cell Biology
Julia Staab, Roswitha Nast, Thomas Meyer
No abstract text is available yet for this article.
September 24, 2018: Immunology and Cell Biology
Xue-Lian Zheng, Jian-Ping Wu, Yue Gong, Jun-Bo Hong, Hai-Ying Xiao, Jia-Wei Zhong, Bo Xie, Bi-Min Li, Gui-Hai Guo, Xuan Zhu, An-Jiang Wang
Interleukin (IL)-25 is a cytokine that has previously been shown to have a protective role against nonalcoholic fatty liver disease (NAFLD), which is associated with the induction of M2 macrophage differentiation. However, the direct relationships between IL-25 expression regulation, M2 induction and NAFLD remain unknown. In this study, we demonstrate that IL-25 promotes hepatic macrophage differentiation into M2a macrophages both in vivo and in vitro via the IL-13/STAT6 pathway. M2 macrophages that were differentiated in vitro were able to ameliorate high-fat diet HFD-induced hepatic steatosis...
September 22, 2018: Immunology and Cell Biology
Seyed Mohammad Gheibi Hayat, Vanessa Bianconi, Matteo Pirro, Amirhossein Sahebkar
During the life of a human being, several tons of apoptotic cells and debris are produced. These apoptotic particles should be cleared quickly and accurately from the body, as they may lose their membrane integrity with the probability of leakage of cytotoxic materials and other intracellular antigens into the environment. The action of removing apoptotic particles occurs by a process called efferocytosis. Efferocytosis is a highly regulated balance among a set of find-me, eat-me and don't-eat-me signals. Efferocytosis is accompanied by a suppression of the immune system that can explain its negative role in cancer...
September 19, 2018: Immunology and Cell Biology
Ailin Lepletier, Viviana P Lutzky, Deepak Mittal, Kimberley Stannard, Thomas S Watkins, Champa N Ratnatunga, Corey Smith, Helen M McGuire, Roslyn A Kemp, Pamela Mukhopadhyay, Nicola Waddell, Mark J Smyth, William C Dougall, John J Miles
CD96 has recently been shown to be a potent immune checkpoint molecule in mice but a similar role in humans is unknown. In this study we provide a detailed map of CD96 expression across human lymphocyte lineages, the kinetics of CD96 regulation upon T cell activation and co-expression with other conventional and emerging immune checkpoint molecules. We show that CD96 is predominantly expressed by T cells and has a unique lymphocyte expression profile. CD96high T cells exhibited distinct effector functions upon activation...
September 17, 2018: Immunology and Cell Biology
Yi Yang, Di Sun, Ji Zhou, Chensheng Tan, Hong Zhang, ZhengRong Chen, ChuangLi Hao, Jinping Zhang
Myeloid-derived suppressor cells (MDSCs) represent a group of immature myeloid cells composed of myeloid progenitor cells and immature myeloid cells that can negatively regulate immune responses by inhibiting T cell function. In mice, MDSCs are broadly defined by the expression of CD11b and Gr1. We and others have shown that injection of a lethal or sublethal dose of LPS into mice could result in the expansion of MDSCs in the bone marrow(BM), spleen and blood. Until now, the molecular mechanisms responsible for this expansion are poorly studied; specifically, the roles of the individual microRNAs (miRNAs) which may be involved remain largely unknown...
September 17, 2018: Immunology and Cell Biology
Gina J Fiala, Bruno Silva-Santos
No abstract text is available yet for this article.
September 16, 2018: Immunology and Cell Biology
Katarzyna Mikolajewicz, Grzegorz Chodaczek
Several tissue clearing methods have been developed for three-dimensional imaging of thick specimens. Here, we applied CUBIC and ScaleS approaches to whole-mounted vaginal wall to reveal spatial distribution of γδ T lymphocytes, the key cells engaged in the epithelial homeostasis control and immune surveillance. Both methods rendered the tissue transparent and enabled detection of the green fluorescent protein (GFP)-expressing γδ T cells in vaginal samples of Tcrd-H2BeGFP transgenic mice. Upon additional immunolabeling, however, only CUBIC preserved the GFP signal and allowed for cell localization assessment during the estrous cycle...
September 14, 2018: Immunology and Cell Biology
Chenming Wu, Ang Li, Jian Hu, Jiuhong Kang
The role of specific histone deacetylase (HDAC) proteins in regulating the lipopolysaccharide (LPS)-induced inflammatory response and its underlying mechanisms are unclear. Here, HDAC2, a class I HDAC family protein, is essential for the LPS-triggered inflammatory response in macrophages. LPS stimulation increases HDAC2 expression in macrophages. Knockdown of HDAC2 decreases the expression of proinflammatory genes, such as IL-12, TNF-α and iNOS following stimulation with LPS. The adoptive transfer of HDAC2 knockdown macrophages attenuates the LPS-triggered innate inflammatory response in vivo, and these mice are less sensitive to endotoxin shock and Escherichia coli-induced sepsis...
September 12, 2018: Immunology and Cell Biology
Juming Yan, Daniel J Cua, Michele Wl Teng
No abstract text is available yet for this article.
September 8, 2018: Immunology and Cell Biology
Jane A Mullaney, Juliette E Stephens, Brooke E Geeling, Emma E Hamilton-Williams
The microbial community making up the gut microbiota can profoundly influence intestinal homeostasis and immune system development, and is believed to influence the development of complex diseases including type 1 diabetes (T1D). T1D susceptible nonobese diabetic (NOD) mice have been shown to harbor a distinct microbiota to disease-protected mice. We hypothesized that the T1D susceptible genetic background of NOD mice would be resistant to the introduction of a C57BL/6-derived microbiota. NOD and C57BL/6 mice were cohoused either continually from birth, from birth until weaning or from weaning onwards, allowing transfer of microbiota between the mice...
September 7, 2018: Immunology and Cell Biology
Pierre C McCarthy, Iain R Phair, Corinna Greger, Katerina Pardali, Victoria A McGuire, Andrew R Clark, Matthias Gaestel, J Simon C Arthur
IL-33 is an IL-1-related cytokine that can act as an alarmin when released from necrotic cells. Once released it can target various immune cells including mast cells, innate lymphoid cells and T cells to elicit a Th2-like immune response. We show here that bone marrow derived mast cells produce IL-13, IL-6, TNF, GM-CSF, CCL3 and CCL4 in response to IL-33 stimulation. Inhibition of the p38 MAPK, or inhibition or knockout of its downstream kinases MK2 and MK3, blocked the production of these cytokines in response to IL-33...
September 1, 2018: Immunology and Cell Biology
Hazel C Poyntz, Angela Jones, Ruy Jauregui, Wayne Young, Aurélie Gestin, Anna Mooney, Olivier Lamiable, Eric Altermann, Alfonso Schmidt, Olivier Gasser, Laura Weyrich, Chris J Jolly, Michelle A Linterman, Graham Le Gros, Edwin D Hawkins, Elizabeth Forbes-Blom
Antibody-mediated immunity is highly protective against disease. The majority of current vaccines confer protection through humoral immunity, but there is high variability in responsiveness across populations. Identifying immune mechanisms that mediate low antibody responsiveness may provide potential strategies to boost vaccine efficacy. Here, we report diverse antibody responsiveness to unadjuvanted as well as adjuvanted immunization in substrains of BALB/c mice, resulting in high and low antibody response phenotypes...
August 28, 2018: Immunology and Cell Biology
Payam Zarin, Tracy Sh In, Edward Ly Chen, Jastaranpreet Singh, Gladys W Wong, Mahmood Mohtashami, David L Wiest, Michele K Anderson, Juan Carlos Zúñiga-Pflücker
γδ T-cells perform a wide range of tissue- and disease-specific functions that are dependent on the effector cytokines produced by these cells. However, the aggregate signals required for the development of interferon-γ (IFNγ) and interleukin-17 (IL-17) producing γδ T-cells remain unknown. Here, we define the cues involved in the functional programming of γδ T-cells, by examining the roles of T-cell receptor (TCR), Notch, and cytokine-receptor signaling. KN6 γδTCR-transduced Rag2-/- T-cell progenitors were cultured on stromal cells variably expressing TCR and Notch ligands, supplemented with different cytokines...
October 2018: Immunology and Cell Biology
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