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Immunology and Cell Biology

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https://www.readbyqxmd.com/read/28611475/murine-lrba-deficiency-causes-ctla-4-deficiency-in-tregs-without-progression-to-immune-dysregulation
#1
Deborah Burnett, Ian Parish, Etienne Masle-Farquhar, Robert Brink, Christopher Goodnow
Inherited mutations in Lipopolysaccharide Responsive Beige-like Anchor (LRBA) cause a recessive human immune dysregulation syndrome with memory B cell and antibody deficiency (common variable immunodeficiency, CVID), inflammatory bowel disease, enlarged spleen and lymph nodes, accumulation of activated T cells, and multiple autoimmune diseases. To understand the pathogenesis of the syndrome, C57BL/6 mice carrying a homozygous truncating mutation in Lrba were produced using CRISPR/Cas9-mediated gene targeting...
June 14, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28611474/p38%C3%AE-regulates-cytokine-induced-ifn%C3%AE-secretion-via-the-mnk1-eif4e-pathway-in-th1-cells
#2
María Salvador-Bernáldez, Sara B Mateus, Iván Del Barco Barrantes, Simon C Arthur, Carlos Martínez-A, Angel R Nebreda, Jesús M Salvador
The p38 mitogen-activated protein kinase (MAPK) pathway is involved in the regulation of immune and inflammatory processes. We used p38α-conditional, p38β-deficient, and p38α/β double-null mouse models to address the role of these two p38 MAPK in CD4(+) T cells, and found that p38α deficiency causes these cells to hyperproliferate. Our studies indicate that both p38α and p38β are dispensable for T helper cell type 1 (Th1) differentiation but, by controlling IFNγ and TNFα production, are critical for normal Th1 effector function...
June 14, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28611473/apc-targeted-proinsulin-expression-inactivates-insulin-specific-memory-cd8-t-cells-in-nod-mice
#3
Peta Ls Reeves, Rajeev Rudraraju, Xiao Liu, F Susan Wong, Emma E Hamilton-Williams, Raymond J Steptoe
Type 1 diabetes (T1D) results from T-cell mediated autoimmune destruction of pancreatic β cells. Effector T-cell responses emerge early in disease development and expand as disease progresses. Following β cell destruction, a long-lived T-cell memory is generated that represents a barrier to islet transplantation and other cellular insulin-replacement therapies. Development of effective immunotherapies that control or ablate β cell destructive effector and memory T cell responses has the potential to prevent disease progression and recurrence...
June 14, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28611472/cd11a-icam-1-blockade-combined-with-il-2-targeting-therapy-causes-a-paradoxical-acceleration-of-type-1-diabetes
#4
Ekua W Brenu, Timothy J Bartley, Casey M Wright, Emma Hamilton-Williams
Enhancement of regulatory T cell (Treg) function is the goal of many immunotherapies aimed at treating type 1 diabetes (T1D). The use of IL-2 is hindered by its effects on other populations such as effector T cells and NK cells. Combination therapies aimed at suppressing effector T cells while using IL-2 to expand Tregs could be beneficial and have been trialed in T1D patients. We have investigated a combination therapy using IL-2 and αCD11a blocking antibody to simultaneously expand Tregs and suppress the activation and migration of autoreactive T cells...
June 14, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28529324/a-novel-combination-strategy-for-effectively-targeting-cancer-stem-like-cells
#5
Paul A Beavis, Emma V Petley, Phillip K Darcy
No abstract text is available yet for this article.
June 6, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28559542/march9-mediated-ubiquitination-regulates-mhc-i-export-from-the-tgn
#6
Francesca De Angelis Rigotti, Aude De Gassart, Carina Pforr, Florencia Cano, Prudence N'Guessan, Alexis Combes, Voahirana Camossetto, Paul Lehner, Philippe Pierre, Evelina Gatti
Given the heterogeneous nature of antigens, MHC-I intracellular transport intersects with multiple degradation pathways for efficient peptide loading and presentation to cytotoxic T cells. MHC-I loading with peptides in the endoplasmic reticulum (ER) is a tightly regulated process, while post-ER intracellular transport is considered to occur by default, leading to peptide-bearing MHC-I delivery to the plasma membrane. We show here that MHC-I traffic is submitted to a previously uncharacterized sorting step at the trans Golgi network (TGN), dependent on the ubiquitination of its cytoplasmic tail lysine residues...
May 31, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28546550/human-igg2-and-igg4-expressing-memory-b-cells-display-enhanced-molecular-and-phenotypic-signs-of-maturity-and-accumulate-with-age
#7
Britt G de Jong, Hanna IJspeert, Lemelinda Marques, Mirjam van der Burg, Jacques J M van Dongen, Bruno G Loos, Menno C van Zelm
The mechanisms involved in sequential immunoglobulin (IG)G class switching are still largely unknown. Sequential IG class switching is linked to higher levels of somatic hypermutation (SHM) in vivo, but it remains unclear if these are generated temporally during an immune response or upon activation in a secondary response. We here aimed to uncouple these processes and to distinguish memory B cells from primary and secondary immune responses. SHM levels and IgG subclasses were studied with 454 pyrosequencing on PBMC from young children and adults as models for primary and secondary immunological memory...
May 26, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28546549/restimulation-induced-t-cell-death-through-ntb-a-sap-signaling-pathway-is-impaired-in-tuberculosis-patients-with-depressed-immune-responses
#8
Rodrigo E Hernández Del Pino, Joaquín M Pellegrini, Ana I Rovetta, Delfina Peña, Guadalupe I Álvarez, Agustín Rolandelli, Rosa M Musella, Domingo J Palmero, Alejandro Malbran, Virginia Pasquinelli, Verónica E García
Production of IFN-γ contributes to host defense against Mycobacterium tuberculosis (Mtb) infection. We previously demonstrated that Signaling lymphocytic activation molecule-associated protein (SAP) expression on cells from tuberculosis (TB) patients was inversely correlated with IFN-γ production. Here we first investigated the role of NK, T and B cell antigen (NTB-A)/SAP pathway in the regulation of Th1 response against Mtb. Upon antigen stimulation, NTB-A phosphorylation rapidly increases and afterwards modulates IFN-γ and IL-17 secretion...
May 26, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28534503/tumour-vessel-normalization-and-immune-checkpoint-blockade-a-new-synergism
#9
Ruth Ganss
No abstract text is available yet for this article.
May 23, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28529323/an-immunogenic-phenotype-in-paternal-antigen-specific-cd8-t-cells-at-embryo-implantation-elicits-later-fetal-loss-in-mice
#10
Lachlan M Moldenhauer, Kerrilyn R Diener, John D Hayball, Sarah A Robertson
Central to pregnancy success is a state of T cell tolerance to paternal antigens, which is initiated at conception. The role and regulation of specific phenotypes of CD8(+) T cells in mediating pregnancy tolerance is not clear. This study aimed to investigate the impact on pregnancy outcome of altering the cytokine environment during maternal CD8(+) T cell priming in early pregnancy. Transgenic Act-mOVA male mice were mated to C57BL/6 (B6) females to generate fetuses expressing ovalbumin (OVA) as a model paternal antigen...
May 22, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28508894/factoring-in-cd4-t-cells-during-treatment-of-hiv
#11
Jonathan M Coquet
No abstract text is available yet for this article.
May 16, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28485382/single-cell-profiling-of-lineage-determining-transcription-factors-in-antigen-specific-cd4-t-cells-reveals-unexpected-complexity-in-recall-responses-during-immune-reconstitution
#12
Chansavath Phetsouphanh, Yin Xu, Mee Ling Munier, John J Zaunders, Anthony D Kelleher
Recent studies of protein and gene expression at the single-cell level have revealed that the memory T-cell compartment is more heterogeneous than previously acknowledged. Identifying different T helper subsets involved in memory responses at the single-cell level is thus necessary to understand the level of heterogeneity within this population. Antigen-specific CD4(+) T cells were measured using the CD25/OX40 assay together with a qualitative multiplex single-cell RT-PCR assay. Transcription profiles and subset proportions within the antigen-specific CD4(+) T-cell population were dissected...
May 9, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28405017/lectin-pathway-factors-in-patients-suffering-from-juvenile-idiopathic-arthritis
#13
Katarzyna Kasperkiewicz, Łukasz Eppa, Anna S Świerzko, Marcin A Bartłomiejczyk, Zbigniew M Żuber, Katarzyna Siniewicz-Luzeńczyk, Elżbieta Mężyk, Misao Matsushita, Leokadia Bąk-Romaniszyn, Krzysztof Zeman, Mikael Skurnik, Maciej Cedzyński
Both complement activation and certain infections (including those with Yersinia sp.) may contribute to the pathogenesis of juvenile idiopathic arthritis (JIA). We investigated factors specific for the lectin pathway of complement: mannose-binding lectin (MBL), ficolins and MBL-associated serine protease-2 (MASP-2), in 144 patients and 98 controls. One hundred and six patients had oligoarticular disease and 38 had polyarticular disease. In 51 patients (out of 133 tested), Yersinia-reactive antibodies were found (JIA Ye(+) group)...
May 9, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28392557/in-vitro-tracking-and-intracellular-protein-distribution-in-immunology
#14
REVIEW
Kajal Zibaei, Sarah M Russell
New imaging techniques have enabled major advances in understanding how immune reactions are initiated, coordinated and controlled. Imaging methods, which were previously mostly descriptive and supplementary to more quantitative approaches, have now reached sufficient precision and throughput that they are becoming integral to almost all aspects of immunology research. Imaging methodologies that increase the resolution and sensitivity of detection, alongside an ever-expanding range of fluorescent reporters of molecular and cellular activity, and vastly improved analysis methods, have all facilitated this transformation...
May 9, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28377613/follistatin-like-protein-1-modulates-il-17-signaling-via-il-17rc-regulation-in-stromal-cells
#15
Brian T Campfield, Taylor Eddens, Matthew Henkel, Martin Majewski, William Horne, Yury Chaly, Sarah L Gaffen, Raphael Hirsch, Jay K Kolls
Follistatin-like protein 1 (FSTL-1) possesses several newly identified roles in mammalian biology, including interleukin (IL)-17-driven inflammation, though the mechanism underlying FSTL-1 influence on IL-17-mediated cytokine production is unknown. Using parallel in vitro bone marrow stromal cell models of FSTL-1 suppression, we employed unbiased microarray analysis to identify FSTL-1-regulated genes and pathways that could influence IL-17-dependent production of IL-6 and granulocyte colony-stimulating factor...
May 9, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28356569/synergistic-targeting-of-breast-cancer-stem-like-cells-by-human-%C3%AE-%C3%AE-t-cells-and-cd8-t-cells
#16
Hung-Chang Chen, Noémie Joalland, John S Bridgeman, Fouad S Alchami, Ulrich Jarry, Mohd Wajid A Khan, Luke Piggott, Yasmin Shanneik, Jianqiang Li, Marco J Herold, Thomas Herrmann, David A Price, Awen M Gallimore, Richard W Clarkson, Emmanuel Scotet, Bernhard Moser, Matthias Eberl
The inherent resistance of cancer stem cells (CSCs) to existing therapies has largely hampered the development of effective treatments for advanced malignancy. To help develop novel immunotherapy approaches that efficiently target CSCs, an experimental model allowing reliable distinction of CSCs and non-CSCs was set up to study their interaction with non-MHC-restricted γδ T cells and antigen-specific CD8(+) T cells. Stable lines with characteristics of breast CSC-like cells were generated from ras-transformed human mammary epithelial (HMLER) cells as confirmed by their CD44(hi) CD24(lo) GD2(+) phenotype, their mesenchymal morphology in culture and their capacity to form mammospheres under non-adherent conditions, as well as their potent tumorigenicity, self-renewal and differentiation in xenografted mice...
May 9, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28465508/cd8-t-cells-contribute-to-lacrimal-gland-pathology-in-the-nonobese-diabetic-mouse-model-of-sj%C3%A3-gren-syndrome
#17
Jennifer Y Barr, Xiaofang Wang, David K Meyerholz, Scott M Lieberman
Sjögren syndrome is an autoimmune disease characterized by targeted destruction of the lacrimal and salivary glands resulting in symptoms of severe ocular and oral dryness. Despite its prevalence, the mechanisms driving autoimmune manifestations are unclear. In patients and in the nonobese diabetic (NOD) mouse model of Sjögren syndrome, lymphocytic infiltrates consist of CD4 and CD8 T cells, although the role of CD8 T cells in disease pathogenesis has been largely unexplored. Here, we evaluated the contribution of CD8 T cells to lacrimal and salivary gland autoimmunity...
May 3, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28462950/t-cell-activation-rhogtpase-activating-protein-plays-an-important-role-in-th17-cell-differentiation
#18
Norimasa Tamehiro, Kyoko Nishida, Reiko Yanobu-Takanashi, Motohito Goto, Tadashi Okamura, Harumi Suzuki
T-cell activation RhoGTPase-activating protein (TAGAP) is a GTPase-activating protein specific for RhoA that is exclusively expressed in activated T cells. Genome-wide association studies and metagenome SNPs analyses have indicated that TAGAP is associated with the pathogenesis of multiple autoimmune diseases, including psoriasis, rheumatoid arthritis, Crohn's disease, celiac disease and multiple sclerosis. However, the precise function of TAGAP remains unclear. Because TH17 cells contribute to TAGAP-associated autoimmune diseases, we hypothesized that TAGAP plays key roles in the differentiation and/or function of TH17 cells...
May 2, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28446796/the-reinvention-of-twentieth-century-microscopy-for-three-dimensional-imaging
#19
REVIEW
Lachlan W Whitehead, Kate McArthur, Niall D Geoghegan, Kelly L Rogers
In just over a decade, the field of biomedical research has witnessed a radical evolution in technologies for the 3- and 4-dimensional imaging of biological samples. Light sheet fluorescence microscopy is quickly developing into a powerful approach for fast, volumetric imaging of cells, tissues and living organisms. This review touches on the development of 3-dimensional imaging, from its foundations, namely from the invention of confocal microscopy in the twentieth century to more recent examples, notably the IsoView SPIM, the Lattice Light Sheet Microscope and swept confocally aligned planar excitation...
April 27, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28356570/idiopathic-pulmonary-fibrosis-and-a-role-for-autoimmunity
#20
REVIEW
Gerard F Hoyne, Hannah Elliott, Steven E Mutsaers, Cecilia M Prêle
Idiopathic pulmonary fibrosis (IPF) is the most common of the idiopathic interstitial pneumonias. It is typically associated with extensive and progressive fibrosis, and is fatal and has limited treatment options. Characteristically IPF patients display large lymphocyte aggregates composed of CD3(+) T cells and CD20(+) B cells within the lung tissue that are located near sites of active fibrosis. In addition, IPF patients can have autoantibodies to a range of host antigens, suggesting a breakdown in immunological tolerance...
April 25, 2017: Immunology and Cell Biology
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