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https://www.readbyqxmd.com/read/28528702/detailed-characterization-of-mesenchymal-stem-stromal-cells-from-a-large-cohort-of-aml-patients-demonstrates-a-definitive-link-to-treatment-outcomes
#1
Rafael Diaz de la Guardia, Belen Lopez-Millan, Jessie R Lavoie, Clara Bueno, Julio Castaño, Maite Gómez-Casares, Susana Vives, Laura Palomo, Manel Juan, Julio Delgado, Maria L Blanco, Josep Nomdedeu, Alberto Chaparro, Jose Luis Fuster, Eduardo Anguita, Michael Rosu-Myles, Pablo Menéndez
Bone marrow mesenchymal stem/stromal cells (BM-MSCs) are key components of the hematopoietic niche thought to have a direct role in leukemia pathogenesis. BM-MSCs from patients with acute myeloid leukemia (AML) have been poorly characterized due to disease heterogeneity. We report a functional, genetic, and immunological characterization of BM-MSC cultures from 46 AML patients, stratified by molecular/cytogenetics into low-risk (LR), intermediate-risk (IR), and high-risk (HR) subgroups. Stable MSC cultures were successfully established and characterized from 40 of 46 AML patients irrespective of the risk subgroup...
May 18, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28526582/mait-cells-a-tailor-made-mate-in-the-ancient-battle-against-infectious-diseases
#2
REVIEW
Marcela de Lima Moreira, Moriya Tsuji, Alexandra Jane Corbett, Márcio Sobreira Silva Araújo, Andréa Teixeira-Carvalho, Olindo Assis Martins-Filho, Vanessa Peruhype-Magalhães, Jordana Grazziela Coelho-Dos-Reis
It has been almost two decades since the discovery of mucosal-associated invariant T (MAIT)-cells. Several advances in the field have been made such as the discovery of the antimicrobial activity of MAIT-cells, the abundance of these cells in human mucosa and in liver and the discovery of ligands able to bind MR1 and activate MAIT-cells. MAIT-cells are a unique subset of innate-like T-cells that express a canonical T-cell receptor with the alpha chain containing hAV7S2 and AJ33 in humans (TCRVα7.2Jα33) and respond to bacterial/fungus vitamin B2 metabolites by an MR1-dependent pathway...
May 16, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28518215/the-tlr9-signaling-pathway-regulates-mr1-mediated-bacterial-antigen-presentation-in-b-cells
#3
Jianyun Liu, Randy R Brutkiewicz
Mucosal-associated invariant T (MAIT) cells are conserved T cells that express a semi-invariant TCR (Vα7.2 in humans and Vα19 in mice). The development of MAIT cells requires the antigen (Ag) presenting MHC-related protein 1 (MR1), as well as commensal bacteria. The mechanisms that regulate the functional expression of MR1 molecules and their loading with bacterial Ag in APCs are largely unknown. We have found that treating B cells with the TLR9 agonist CpG increases MR1 surface expression. Interestingly, activation of TLR9 by CpG-A (but not CpG-B) enhances MR1 surface expression...
May 18, 2017: Immunology
https://www.readbyqxmd.com/read/28513074/%C3%AE-myrtoxin-mp1a-is-a-helical-heterodimer-from-the-venom-of-the-jack-jumper-ant-with-antimicrobial-membrane-disrupting-and-nociceptive-activities
#4
Zoltan Dekan, Stephen J Heady, Martin Scanlon, Brian A Baldo, Tzong-Hsien Lee, Marie-Isabel Aguilar, Jennifer R Deuis, Irina Vetter, Alysha G Elliott, Maite Amado, Matthew A Cooper, Dianne Alewood, Paul Francis Alewood
Δ-Myrtoxin-Mp1a (Mp1a), a 49-residue heterodimeric peptide from the venom of Myrmecia pilosula is comprised of a 26-mer A chain and a 23-mer B chain connected by two disulfide bonds in an antiparallel arrangement. Combination of the individual synthetic chains via aerial oxidation remarkably resulted in the self-assembly of Mp1a as a homogenous product without the need for directed disulfide bond formation. NMR analysis revealed a well-defined, unique structure containing a pair of antiparallel α-helices...
May 17, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28494326/mait-cells-and-mr1-antigen-recognition
#5
REVIEW
Andrew N Keller, Alexandra J Corbett, Jacinta M Wubben, James McCluskey, Jamie Rossjohn
Mucosal-associated invariant T cells (MAIT cells) are innate-like T cells that recognise antigens presented by the monomorphic MHC-I related molecule, MR1. Distinct from the conventional MHC-restricted T cell system, MR1 presents small-molecule precursors, derived from microbial biosynthesis of riboflavin, to activate the innate MAIT cell effector potential. Recent data demonstrates how: vitamin B precursors modulate intracellular trafficking of MR1 and impact on MAIT cell development; variation in the MAIT cell antigen receptor sequence impacts MR1-antigen recognition; and most notably, how MR1 can capture chemical identities distinct from riboflavin precursors, including drugs and drug-like molecules...
May 8, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28487696/natural-killer-cells-in-graft-versus-host-disease-after-allogeneic-hematopoietic-cell-transplantation
#6
REVIEW
Federico Simonetta, Maite Alvarez, Robert S Negrin
Allogeneic hematopoietic cell transplantation (HCT) is a well-established therapeutic modality effective for a variety of hematological malignancies but, unfortunately, is associated with significant morbidity and mortality related to cancer relapse as well as to transplant-related complications including graft-versus-host-disease (GvHD). Natural killer (NK) cells are the first donor-derived lymphocyte subset to recover after HCT, and their crucial role in protection against cancer relapse and infections is well established...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28485401/foxp3-regulatory-t-cells-maintain-the-bone-marrow-microenvironment-for-b-cell-lymphopoiesis
#7
Antonio Pierini, Hidekazu Nishikii, Jeanette Baker, Takaharu Kimura, Hye-Sook Kwon, Yuqiong Pan, Yan Chen, Maite Alvarez, William Strober, Andrea Velardi, Judith A Shizuru, Joy Y Wu, Shigeru Chiba, Robert S Negrin
Foxp3(+) regulatory T cells (Treg cells) modulate the immune system and maintain self-tolerance, but whether they affect haematopoiesis or haematopoietic stem cell (HSC)-mediated reconstitution after transplantation is unclear. Here we show that B-cell lymphopoiesis is impaired in Treg-depleted mice, yet this reduced B-cell lymphopoiesis is rescued by adoptive transfer of affected HSCs or bone marrow cells into Treg-competent recipients. B-cell reconstitution is abrogated in both syngeneic and allogeneic transplantation using Treg-depleted mice as recipients...
May 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28474257/a-cumulative-effect-involving-malfunction-of-the-pth1r-and-atp4a-genes-explains-a-familial-gastric-neuroendocrine-tumor-with-hypothyroidism-and-arthritis
#8
Oriol Calvete, Maite Herraiz, Jose Reyes, Ana Patiño, Javier Benitez
BACKGROUND: Type I gastric neuroendocrine tumors (gNETs) classically arise because of hypergastrinemia and involve destruction of parietal cells, which are responsible for gastric acid secretion through the ATP4A proton pump and for intrinsic factor production. METHODS: By whole exome sequencing, we studied a family with three members with gNETs plus hypothyroidism and rheumatoid arthritis to uncover their genetic origin. RESULTS: A heterozygous missense mutation in the ATP4A gene was identified...
May 4, 2017: Gastric Cancer
https://www.readbyqxmd.com/read/28470739/vitamin-d-treatment-modulates-immune-activation-in-cystic-fibrosis
#9
Terezia Pincikova, Dominic Paquin-Proulx, Johan K Sandberg, Malin Flodström-Tullberg, Lena Hjelte
Persistent inflammatory response in cystic fibrosis (CF) airways is believed to play a central role in the progression of lung damage. Anti-inflammatory treatment may slow down lung disease progression but adverse side effects have limited its use. Vitamin D has immunoregulatory properties. We randomized 16 CF patients to receive vitamin D2, vitamin D3 or to serve as controls, and investigated the effect of vitamin D supplementation on soluble immunological parameters, myeloid dendritic cells (mDCs) and T cell activation...
May 3, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28442662/possible-involvement-of-mucosal-associated-invariant-t-cells-in-the-progression-of-inflammatory-bowel-diseases
#10
Kentaro Tominaga, Satoshi Yamagiwa, Toru Setsu, Naruhiro Kimura, Hiroki Honda, Hiroteru Kamimura, Yutaka Honda, Masaaki Takamura, Junji Yokoyama, Kenji Suzuki, Toshifumi Wakai, Shuji Terai
Mucosal-associated invariant T (MAIT) cells are innate-like T cells involved in anti-bacterial immunity. Recent studies have demonstrated that MAIT cells might be implicated in inflammatory bowel diseases (IBDs), but their precise function in IBD remains to be elucidated. We investigated the possible involvement of MAIT cells in the immunopathogenesis of IBDs. Heparinized peripheral blood and biopsy specimens of the colon were collected from 25 patients with ulcerative colitis (UC), 15 patients with Crohn's disease (CD), and 19 heathy individuals...
2017: Biomedical Research
https://www.readbyqxmd.com/read/28428786/challenge-of-humans-with-wild-type-salmonella-enterica-serovar-typhi-elicits-changes-in-the-activation-and-homing-characteristics-of-mucosal-associated-invariant-t-cells
#11
Rosângela Salerno-Goncalves, David Luo, Stephanie Fresnay, Laurence Magder, Thomas C Darton, Claire Jones, Claire S Waddington, Christoph J Blohmke, Brian Angus, Myron M Levine, Andrew J Pollard, Marcelo B Sztein
Gastrointestinal infections by Salmonella enterica serovar Typhi (S. Typhi) are rare in industrialized countries. However, they remain a major public health problem in the developing world with an estimated 26.9 million new cases annually and significant mortality when untreated. Recently, we provided the first direct evidence that CD8(+) MAIT cells are activated and have the potential to kill cells exposed to S. Typhi, and that these responses are dependent on bacterial load. However, MAIT cell kinetics and function during bacterial infections in humans remain largely unknown...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28421059/phages-in-the-human-body
#12
REVIEW
Ferran Navarro, Maite Muniesa
Bacteriophages, viruses that infect bacteria, have re-emerged as powerful regulators of bacterial populations in natural ecosystems. Phages invade the human body, just as they do other natural environments, to such an extent that they are the most numerous group in the human virome. This was only revealed in recent metagenomic studies, despite the fact that the presence of phages in the human body was reported decades ago. The influence of the presence of phages in humans has yet to be evaluated; but as in marine environments, a clear role in the regulation of bacterial populations could be envisaged, that might have an impact on human health...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28419492/expression-and-trafficking-of-mhc-related-protein-1-mr1
#13
REVIEW
R Lamichhane, J E Ussher
MHC related protein 1 (MR1) is a non-polymorphic MHC class IB antigen presenting molecule that is the restricting molecule for mucosal associated invariant T (MAIT) cells, a prominent population of innate-like antibacterial T cells. The MAIT cell-MR1 axis represents a new paradigm in antigen presentation, with the MR1 ligand derived from vitamin B compounds or their metabolic precursors. Many bacteria and some fungi produce the activating ligand for MR1. In evolution, MR1 is highly conserved in most, but not all, mammals...
April 17, 2017: Immunology
https://www.readbyqxmd.com/read/28387217/defective-gpsm2-g%C3%AE-i3-signalling-disrupts-stereocilia-development-and-growth-cone-actin-dynamics-in-chudley-mccullough-syndrome
#14
Stephanie A Mauriac, Yeri E Hien, Jonathan E Bird, Steve Dos-Santos Carvalho, Ronan Peyroutou, Sze Chim Lee, Maite M Moreau, Jean-Michel Blanc, Aysegul Geyser, Chantal Medina, Olivier Thoumine, Sandra Beer-Hammer, Thomas B Friedman, Lukas Rüttiger, Andrew Forge, Bernd Nürnberg, Nathalie Sans, Mireille Montcouquiol
Mutations in GPSM2 cause Chudley-McCullough syndrome (CMCS), an autosomal recessive neurological disorder characterized by early-onset sensorineural deafness and brain anomalies. Here, we show that mutation of the mouse orthologue of GPSM2 affects actin-rich stereocilia elongation in auditory and vestibular hair cells, causing deafness and balance defects. The G-protein subunit Gαi3, a well-documented partner of Gpsm2, participates in the elongation process, and its absence also causes hearing deficits. We show that Gpsm2 defines an ∼200 nm nanodomain at the tips of stereocilia and this localization requires the presence of Gαi3, myosin 15 and whirlin...
April 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/28384290/mait-cells-are-reduced-in-frequency-and-functionally-impaired-in-human-t-lymphotropic-virus-type-1-infection-potential-clinical-implications
#15
Dominic Paquin-Proulx, Benjamin C Greenspun, Emanuela A S Costa, Aluisio C Segurado, Esper G Kallas, Douglas F Nixon, Fabio E Leal
HTLV-1 infection is associated with several inflammatory disorders, including the neurodegenerative condition HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). It is unclear why a minority of infected subjects develop HAM/TSP. The cellular immune response has been implicated in the development of inflammatory alterations in these patients; however the pathogenic mechanisms for disease progression remain unclear. Furthermore, HTLV-1-infected individuals have an increase incidence of Mycobacterium tuberculosis (Mtb) infection, suggesting that immunological defect are associated with HTLV-1 infection...
2017: PloS One
https://www.readbyqxmd.com/read/28378547/deficiencies-of-circulating-mucosal-associated-invariant-t-cells-and-natural-killer-t-cells-in-patients-with-multiple-trauma
#16
Young Goun Jo, Hyun Jung Choi, Jung Chul Kim, Young Nan Cho, Jeong Hwa Kang, Hye Mi Jin, Seung Jung Kee, Yong Wook Park
Mucosal-associated invariant T (MAIT) cells and natural killer T (NKT) cells are known to play important roles in autoimmunity, infectious diseases and cancers. However, little is known about the roles of these invariant T cells in multiple trauma. The purposes of this study were to examine MAIT and NKT cell levels in patients with multiple trauma and to investigate potential relationships between these cell levels and clinical parameters. The study cohort was composed of 14 patients with multiple trauma and 22 non-injured healthy controls (HCs)...
May 2017: Journal of Korean Medical Science
https://www.readbyqxmd.com/read/28370104/recent-advances-in-gut-immunology
#17
Nick Powell, Thomas T MacDonald
In recent years there have been significant advances in our understanding of the mucosal immune system. In addition to unravelling some of the complexities of this system, including the discovery of completely new cells types, further insights into the three way interactions between mucosal immune cells, the intestinal epithelium and the microbial communities colonizing the GI tract, promises to redefine our understanding of how intestinal homeostasis is maintained, but also how dysregulation of these highly integrated interactions conspires to cause disease...
March 31, 2017: Parasite Immunology
https://www.readbyqxmd.com/read/28355272/vitamin-d-receptor-gene-is-epigenetically-altered-and-transcriptionally-up-regulated-in-multiple-sclerosis
#18
Teresa Ayuso, Patricia Aznar, Luis Soriano, Ander Olaskoaga, Miren Roldán, María Otano, Iratxe Ajuria, Gerardo Soriano, Francisco Lacruz, Maite Mendioroz
OBJECTIVE: Vitamin D deficiency has been linked to increased risk of multiple sclerosis (MS) and poor outcome. However, the specific role that vitamin D plays in MS still remains unknown. In order to identify potential mechanisms underlying vitamin D effects in MS, we profiled epigenetic changes in vitamin D receptor (VDR) gene to identify genomic regulatory elements relevant to MS pathogenesis. METHODS: Human T cells derived from whole blood by negative selection were isolated in a set of 23 relapsing-remitting MS (RRMS) patients and 12 controls matched by age and gender...
2017: PloS One
https://www.readbyqxmd.com/read/28346544/epigenetic-silencing-of-v-d-j-recombination-is-a-major-determinant-for-selective-differentiation-of-mucosal-associated-invariant-t-cells-from-induced-pluripotent-stem-cells
#19
Yutaka Saito, Chie Sugimoto, Toutai Mituyama, Hiroshi Wakao
Mucosal-associated invariant T cells (MAITs) are innate-like T cells that play a pivotal role in the host defense against infectious diseases, and are also implicated in autoimmune diseases, metabolic diseases, and cancer. Recent studies have shown that induced pluripotent stem cells (iPSCs) derived from MAITs selectively redifferentiate into MAITs without altering their antigen specificity. Such a selective differentiation is a prerequisite for the use of MAITs in cell therapy and/or regenerative medicine...
2017: PloS One
https://www.readbyqxmd.com/read/28328117/noonan-syndrome-ptpn11-mutations-and-brain-tumors-a-clinical-report-and-review-of-the-literature
#20
Aurore Siegfried, Claude Cances, Marie Denuelle, Najat Loukh, Maïté Tauber, Hélène Cavé, Marie-Bernadette Delisle
Noonan syndrome (NS), an autosomal dominant disorder, is characterized by short stature, congenital heart defects, developmental delay, and facial dysmorphism. PTPN11 mutations are the most common cause of NS. PTPN11 encodes a non-receptor protein tyrosine phosphatase, SHP2. Hematopoietic malignancies and solid tumors are associated with NS. Among solid tumors, brain tumors have been described in children and young adults but remain rather rare. We report a 16-year-old boy with PTPN11-related NS who, at the age of 12, was incidentally found to have a left temporal lobe brain tumor and a cystic lesion in the right thalamus...
April 2017: American Journal of Medical Genetics. Part A
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