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Immunology and Cell Biology

Patricia M Benveniste, Munehide Nakatsugawa, Linh Nguyen, Pamela S Ohashi, Naoto Hirano, Juan Carlos Zúñiga-Pflücker
The differentiation of human hematopoietic stem cells into CD8 T cells can be achieved in vitro with the OP9-DL4 system. We considered that in the absence of thymic medullary epithelial cells, which serve to restrict the breath of the T-cell receptor (TCR) repertoire by expressing tissue-restricted antigens, a distinct repertoire would be generated in vitro. To test this notion, we compared the TCR-Vα/Vβ (TRAV/TRBV) gene usage of major histocompatibility complex (MHC)-restricted antigen (MART-1) specific T-cells generated in vitro to that from ex vivo naïve T cells and tumour-infiltrating lymphocytes (TILs) using high-throughput DNA sequencing...
January 11, 2019: Immunology and Cell Biology
Emily M Mulcahy, Margaret A Cooley, Helen McGuire, Suzanne Asad, Barbara Fazekas de St Groth, Sean A Beggs, Louise F Roddam
Cystic fibrosis (CF) is caused by mutations to the CF transmembrane conductance regulator (CFTR) gene. The CFTR is known to be expressed on multiple immune cell subtypes, dendritic cells (DCs), monocytes/macrophages, neutrophils and lymphocytes. We hypothesised that lack of CFTR expression on peripheral blood innate immune cells would result in an altered cell profile in the periphery and that this profile would reflect lung pathology. We performed a flow cytometric phenotypic investigation of innate immune cell proportions in peripheral blood collected from 17 CF patients and 15 age-matched healthy controls...
January 11, 2019: Immunology and Cell Biology
Enwono Eyoh, Patrick McCallum, Justin Killick, Seth Amanfo, Francisca Mutapi, Anne L Astier
Praziquantel (PZQ) is an anthelminthic human and veterinary drug used to treat trematode and cestode worms. Changes in immune responses have been demonstrated in humans following curative PZQ treatment of schistosome infections. These changes have been attributed to the removal of immunosupressive worms and immune responses to parasite antigens exposed from dying worms. To date, there has been no study investigating the potential direct effect of PZQ on the host immune cells. Herein, we analyzed the effect of PZQ on human CD4+ T cells classically costimulated by CD3/CD28 or costimulated by the complement regulator CD46 to induce Type 1 regulatory T cells (Tr1)...
January 8, 2019: Immunology and Cell Biology
Sharesta Khoenkhoen, Elina Erikson, Monika Ádori, Julian M Stark, Jean L Scholz, Michael P Cancro, Gabriel K Pedersen, Gunilla B Karlsson Hedestam
Impaired classical NF-κB pathway signaling causes reduced antibody responses to T-independent (TI) antigens. We investigated potential reasons for defective TI responses in mice lacking the atypical inhibitory kappa B (IκB) protein of the NF-κB pathway, IκBNS. Analyses of the plasma cell compartment in vitro and in vivo after challenge with TI antigen showed significant decreases in the frequencies of plasma cells in the absence of IκBNS. In vitro activation of B cells via the B cell receptor (BCR) or via Toll-like receptor (TLR) 4 revealed that early activation events were unaffected in IκBNS-deficient B cells, while proliferation was reduced compared to in similarly stimulated wildtype (wt) B cells...
December 29, 2018: Immunology and Cell Biology
Sayan Ghosh, Sreetama Choudhury, Sudeshna Mukherjee, Payal Gupta, Olivia Chowdhury, Rathindranath Baral, Sreya Chattopadhyay
Inappropriate functioning of the immune system is observed during sustained systemic inflammation, which might lead to immune deficiencies, autoimmune disorders, and cancer. Primary lymphoid organs may progress to a deregulated proliferative state in response to inflammatory signals in order to intensify host defense mechanisms and exacerbate an inflammatory niche. Fluoxetine, a selective serotonin reuptake inhibitor, has recently been projected as an anti-inflammatory agent. This study had been designed to evaluate the potential novel role of fluoxetine in reversing inflammation-induced immune dysfunction...
December 24, 2018: Immunology and Cell Biology
Feifei Ren, Qitai Zhao, Lan Huang, Yujia Zheng, Lifeng Li, Qianyi He, Chaoqi Zhang, Feng Li, Nomathamsanqa Resegofetse Maimela, Zhi Sun, Qingquan Jia, Yu Ping, Zhen Zhang, Xinfeng Chen, Ying Yue, Shasha Liu, Ling Cao, Yi Zhang
Mutations in the isocitrate dehydrogenase (IDH) 1 gene, especially the R132H mutation, have been reported to be associated with a better prognosis in glioma patients. However, the underlying molecular mechanisms are not yet well understood. Many factors may contribute to differences in the survival of IDH1 wild-type (WT) and IDH1 mutant glioma patients, in which immune components play a potentially important role. In this study, we analyzed The Cancer Genome Atlas (TCGA), and the Chinese Glioma Genome Atlas (CGGA) databases, as well as glioma patient-derived tumor samples...
December 21, 2018: Immunology and Cell Biology
Madeline Gleave Parson, Juanita Grimmett, Jordan K Vance, Michelle R Witt, Brittany G Seman, Travis W Rawson, Logan Lyda, Christopher Labuda, Joo-Yong Jung, Shelby D Bradford, Cory M Robinson
Microbial infections early in life remain a major cause of infant mortality worldwide. This is consistent with immune deficiencies in this population. Interleukin (IL)-27 is suppressive toward a variety of immune cell types, and we have shown that production of IL-27 is elevated in humans and mice early in life. We hypothesize that elevated levels of IL-27 oppose protective responses to infection during the neonatal period. In the present study, we extended previous findings in neonatal mice to identify a population of IL-27 producers that express Gr-1 and were further identified as myeloid-derived suppressor cells (MDSCs) based on expression of surface markers and functional studies...
December 21, 2018: Immunology and Cell Biology
Jacques Miller
Barely 60 years ago, the thymus was considered to be a vestigial organ with no known function or just a graveyard for dying lymphocytes. Now, the thymus and its cells cover a vast area of immunology, genetics and epigenetics relating to medicine, including inflammation, infection, vaccination, dysbiosis, immunodeficiency, allergy, autoimmunity, transplantation, tissue repair, pregnancy and cancer. New technology and approaches, now becoming available, will lead to a much deeper understanding of many of these conditions...
December 18, 2018: Immunology and Cell Biology
Ping Meng, Zhuang-Gui Chen, Tian-Tuo Zhang, Zhuo-Zheng Liang, Xiao-Ling Zou, Hai-Ling Yang, Hong-Tao Li
Interleukin (IL)-37 has been described as a negative regulator of immune responses and is critical for asthma pathogenesis, but the mechanisms behind the protective role of IL-37 against allergic asthma are less well understood. We show here that IL-37 administered intranasally (i.n.) inhibited house dust mite (HDM)-induced chronic airway eosinophilic inflammation, goblet cell hyperplasia, peribronchial collagen deposition and airway hyperresponsiveness (AHR) to methacholine. In contrast to a weakened Th2 response in the lung that was characterized by the downregulation of Th2-associated cytokines and chemokines in IL-37-treated mice, IL-37 has no effect on relevant markers of systemic Th2 immune including serum immunoglobulins expression and in vitro production of Th2-associated cytokines by splenocytes on HDM recall...
December 11, 2018: Immunology and Cell Biology
Katharine J Goodall, Angela Nguyen, Aya Matsumoto, Julie R McMullen, Sidonia B Eckle, Patrick Bertolino, Lucy C Sullivan, Daniel M Andrews
Class Ib MHC are an extended family of molecules which demonstrate tissue-specific expression and presentation of monomorphic antigens. These characteristics tend to imbue class Ib MHC with unique functions. H2-Q10 is potentially one such molecule in that it is overexpressed in the liver but its immunological function is not known. We have previously shown that H2-Q10 is a ligand for the natural killer cell receptor Ly49C and now, using H2-Q10 deficient mice, we demonstrate that H2-Q10 can also stabilize the expression of Qa-1b...
December 9, 2018: Immunology and Cell Biology
Kathleen E Stevens, Chloe L Thio, William O Osburn
Human genetic studies demonstrate a link between the 32-bp deletion that produces a nonfunctional CCR5 receptor (CCR5∆32) and enhanced recovery from acute hepatitis B virus (HBV) infection. To investigate the role of CCR5 in immune responses to acute HBV, we intravenously infected Ccr5+/+ (WT) and Ccr5-/- (KO) mice with a replication-incompetent adenovirus containing the overlapping HBV1.3 construct (AdHBV), or vector control. At day 3 following AdHBV infection, analysis of intrahepatic leukocytes (IHL) showed KO mice had increased CD11b+ NK cells compared to WT (18...
December 8, 2018: Immunology and Cell Biology
R Ahmed, E T Cadman, C M Snapper, R A Lawrence
Brugia malayi is a nematode that causes human lymphatic filariasis. Previously, we showed that mannose binding lectin (MBL) -A is necessary for clearance of B. malayi microfilariae in mice and presence of MBL-A is linked with maximal levels of parasite-specific IgM. Common human MBL gene polymorphisms result in low MBL expression and lead to recurring bacterial infections. Furthermore, these low-expressing human MBL polymorphisms result in greatly increased susceptibility to lymphatic filarial infection. Indeed, gain of new filarial infections over a 30-year period are 10-fold higher in people with low, compared to high, MBL-expression phenotypes...
November 20, 2018: Immunology and Cell Biology
Xiao-Hua Yu, Da-Wei Zhang, Xi-Long Zheng, Chao-Ke Tang
Macrophages play a central role in innate immunity as the first line of defense against pathogen infection. Upon exposure to inflammatory stimuli, macrophages rapidly respond and subsequently undergo metabolic reprogramming to substantially produce cellular metabolites, such as itaconate. As a derivate of the tricarboxylic acid cycle, itaconate is derived from the decarboxylation of cis-aconitate mediated by immunoresponsive gene 1 in the mitochondrial matrix. It is well known that itaconate has a direct anti-microbial effect by inhibiting isocitrate lyase...
November 14, 2018: Immunology and Cell Biology
Alice Ballerie, Alain Lescoat, Yu Augagneur, Marie Lelong, Claudie Morzadec, Claire Cazalets, Stéphane Jouneau, Olivier Fardel, Laurent Vernhet, Patrick Jégo, Valérie Lecureur
A defect in the apoptotic cell clearance (efferocytosis) by phagocytic cells may participate in autoimmunity and chronic inflammation. The mechanisms leading to the emergence of auto-immunity in systemic sclerosis (SSc) are still to be determined. In this study, the efferocytosis capacities of blood monocyte-derived macrophages (MDM) from patients with SSc were evaluated. Blood monocytes obtained from patients with SSc and healthy donors (HD) were differentiated in vitro into macrophages. The capacities of MDM to engulf CFSE+ apoptotic Jurkat human T lymphocytes were compared between SSc MDM and HD using flow cytometry...
November 13, 2018: Immunology and Cell Biology
Delfim Duarte, Saoirse Amarteifio, Heather Ang, Isabella Y Kong, Nicola Ruivo, Gunnar Pruessner, Edwin D Hawkins, Cristina Lo Celso
The majority of acute myeloid leukemia (AML) patients have a poor response to conventional chemotherapy. The survival of chemoresistant cells is thought to depend on leukemia-bone marrow (BM) microenvironment interactions, which are not well understood. The CXCL12/CXCR4 axis has been proposed to support AML growth but was not studied at the single AML cell level. We recently showed that T-cell lymphoblastic leukemia (T-ALL) cells are highly motile in the BM; however, the characteristics of AML cell migration within the BM remain undefined...
November 13, 2018: 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
Paola Cura Daball, Monica Sofia Ventura Ferreira, Sandra Ammann, Christian Klemann, Myriam R Lorenz, Ursula Warthorst, Timothy Ronan Leahy, Niall Conlon, Justin Roche, Pere Soler-Palacín, Marina Garcia-Prat, Ilka Fuchs, Sebastian Fuchs, Fabian Beier, Tim H Brümmendorf, Carsten Speckmann, Peter Olbrich, Olaf Neth, Klaus Schwarz, Stephan Ehl, Anne Rensing-Ehl
Premature T-cell immunosenescence with CD57+ CD8+ T-cell accumulation has been linked to immunodeficiency and autoimmunity in primary immunodeficiencies including activated PI3 kinase delta syndrome (APDS). To address whether CD57 marks the typical senescent T-cell population seen in adult individuals or identifies a distinct population in APDS, we compared CD57+ CD8+ T cells from mostly pediatric APDS patients to those of healthy adults with similarly prominent senescent T cells. CD57+ CD8+ T cells from APDS patients were less differentiated with more CD27+ CD28+ effector memory T cells showing increased PD1 and Eomesodermin expression...
November 2018: Immunology and Cell Biology
Siobhan Crittenden, Ashleigh Cheyne, Alexander Adams, Thorsten Forster, Calum T Robb, Jennifer Felton, Gwo-Tzer Ho, Dominik Ruckerl, Adriano G Rossi, Stephen M Anderton, Peter Ghazal, Jack Satsangi, Sarah E Howie, Chengcan Yao
Inflammatory bowel disease (IBD) is a condition of chronic inflammatory intestinal disorder with increasing prevalence but limited effective therapies. The purine metabolic pathway is involved in various inflammatory processes including IBD. However, the mechanisms through which purine metabolism modulates IBD remain to be established. Here, we found that mucosal expression of genes involved in the purine metabolic pathway is altered in patients with active ulcerative colitis (UC), which is associated with elevated gene expression signatures of the group 3 innate lymphoid cell (ILC3)-interleukin (IL)-22 pathway...
November 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
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