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https://www.readbyqxmd.com/read/29669782/the-respiratory-environment-diverts-the-development-of-antiviral-memory-cd8-t-cells
#1
Hillary L Shane, Katie L Reagin, Kimberly D Klonowski
Our understanding of memory CD8+ T cells has been largely derived from acute, systemic infection models. However, memory CD8+ T cells generated from mucosal infection exhibit unique properties and, following respiratory infection, are not maintained in the lung long term. To better understand how infection route modifies memory differentiation, we compared murine CD8+ T cell responses to a vesicular stomatitis virus (VSV) challenge generated intranasally (i.n.) or i.v. The i.n. infection resulted in greater peak expansion of VSV-specific CD8+ T cells...
April 18, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29652923/limited-immune-surveillance-in-lymphoid-tissue-by-cytolytic-cd4-t-cells-during-health-and-hiv-disease
#2
Marcus Buggert, Son Nguyen, Laura M McLane, Maria Steblyanko, Nadia Anikeeva, Dominic Paquin-Proulx, Perla M Del Rio Estrada, Yuria Ablanedo-Terrazas, Kajsa Noyan, Morgan A Reuter, Korey Demers, Johan Sandberg, Michael A Eller, Hendrik Streeck, Marianne Jansson, Piotr Nowak, Anders Sönnerborg, David H Canaday, Ali Naji, E John Wherry, Merlin Robb, Steven G Deeks, Gustavo Reyes-Teran, Yuri Sykulev, Annika C Karlsson, Michael R Betts
CD4+ T cells subsets have a wide range of important helper and regulatory functions in the immune system. Several studies have specifically suggested that circulating effector CD4+ T cells may play a direct role in control of HIV replication through cytolytic activity or autocrine β-chemokine production. However, it remains unclear whether effector CD4+ T cell populations expressing cytolytic molecules and β-chemokines are present within lymph nodes (LNs), a major site of HIV replication. Here, we report that expression of β-chemokines and cytolytic molecules are enriched within a CD4+ T cell population with high levels of the T-box transcription factors T-bet and eomesodermin (Eomes)...
April 13, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29388193/eomes-positive-cd4-t-cells-are-increased-in-ptpn22-1858t-risk-allele-carriers
#3
Karine Chemin, Daniel Ramsköld, Lina-Marcela Diaz-Gallo, Jessica Herrath, Miranda Houtman, Karolina Tandre, Lars Rönnblom, Anca Catrina, Vivianne Malmström
The presence of the PTPN22 risk allele (1858T) is associated with several autoimmune diseases including rheumatoid arthritis (RA). Despite a number of studies exploring the function of PTPN22 in T cells, the exact impact of the PTPN22 risk allele on T-cell function in humans is still unclear. In this study, using RNA sequencing, we show that, upon TCR-activation, naïve human CD4+ T cells homozygous for the PTPN22 risk allele overexpress a set of genes including CFLAR and 4-1BB, which are important for cytotoxic T-cell differentiation...
January 31, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29382828/cardiogenic-programming-of-human-pluripotent-stem-cells-by-dose-controlled-activation-of-eomes
#4
Martin J Pfeiffer, Roberto Quaranta, Ilaria Piccini, Jakob Fell, Jyoti Rao, Albrecht Röpke, Guiscard Seebohm, Boris Greber
Master cell fate determinants are thought to induce specific cell lineages in gastrulation by orchestrating entire gene programs. The T-box transcription factor EOMES (eomesodermin) is crucially required for the development of the heart-yet it is equally important for endoderm specification suggesting that it may act in a context-dependent manner. Here, we define an unrecognized interplay between EOMES and the WNT signaling pathway in controlling cardiac induction by using loss and gain-of-function approaches in human embryonic stem cells...
January 30, 2018: Nature Communications
https://www.readbyqxmd.com/read/29319368/association-of-increased-eomesodermin-bcl6-and-granzyme-b-expression-with-major-clinical-manifestations-of-hashimoto-s-thyroiditis-an-observational-study
#5
Mario Štefanić, Stana Tokić, Mirjana Suver Stević, Ljubica Glavaš-Obrovac
PURPOSE: Studies of cytotoxic T cells and their respective lineage master regulators have been limited in Hashimoto's thyroiditis (HT). It is unclear whether their transcriptomes are changed in HT patients and how these changes are associated with the thyroid damage, major clinical manifestations, and disease progression. METHODS: We explored the gene expression patterns of selected transcription factors [eomesodermin (EOMES), BACH2, BCL6, TCF1] and cytolytic molecules [granzyme B (GZMB)] in peripheral blood (PB) T cells of 10 healthy controls and 30 HT patients of various subtypes (hypothyroid, untreated HT; L-thyroxine (T4)-treated HT, and spontaneously euthyroid HT) using real-time quantitative PCR...
April 2018: Immunological Investigations
https://www.readbyqxmd.com/read/29305435/an-immunotherapeutic-cd137-agonist-releases-eomesodermin-from-thpok-repression-in-cd4-t-cells
#6
Payal Mittal, Rebecca Abblett, Joseph M Ryan, Adam T Hagymasi, Archibald Agyekum-Yamoah, Julia Svedova, Steven L Reiner, Marie-Clare St Rose, Matthew P Hanley, Anthony T Vella, Adam J Adler
Agonists to the TNF/TNFR costimulatory receptors CD134 (OX40) and CD137 (4-1BB) elicit antitumor immunity. Dual costimulation with anti-CD134 plus anti-CD137 is particularly potent because it programs cytotoxic potential in CD8+ and CD4+ T cells. Cytotoxicity in dual-costimulated CD4 T cells depends on the T-box transcription factor eomesodermin (Eomes), which we report is induced via a mechanism that does not rely on IL-2, in contrast to CD8+ CTL, but rather depends on the CD8 T cell lineage commitment transcription factor Runx3, which supports Eomes expression in mature CD8+ CTLs...
February 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29302250/lineage-differentiation-program-of-invariant-natural-killer-t-cells
#7
REVIEW
Dong-Il Kwon, You Jeong Lee
Invariant natural killer T (iNKT) cells are innate T cells restricted by CD1d molecules. They are positively selected in the thymic cortex and migrate to the medullary area, in which they differentiate into 3 different lineages. Promyelocytic leukemia zinc finger (PLZF) modulates this process, and PLZFhigh , PLZFintermediate , and PLZFlow iNKT cells are designated as NKT2, NKT17, and NKT1 cells, respectively. Analogous to conventional helper CD4 T cells, each subset expresses distinct combinations of transcription factors and produces different cytokines...
December 2017: Immune Network
https://www.readbyqxmd.com/read/29296921/interleukins-12-and-15-induce-cytotoxicity-and-early-nk-cell-differentiation-in-type-3-innate-lymphoid-cells
#8
Ana Raykova, Paolo Carrega, Frank M Lehmann, Robert Ivanek, Vanessa Landtwing, Isaak Quast, Jan D Lünemann, Daniela Finke, Guido Ferlazzo, Obinna Chijioke, Christian Münz
Type 3 innate lymphoid cells (ILC3s) fulfill protective functions at mucosal surfaces via cytokine production. Although their plasticity to become ILC1s, the innate counterparts of type 1 helper T cells, has been described previously, we report that they can differentiate into cytotoxic lymphocytes with many characteristics of early differentiated natural killer (NK) cells. This transition is promoted by the proinflammatory cytokines interleukin 12 (IL-12) and IL-15, and correlates with expression of the master transcription factor of cytotoxicity, eomesodermin (Eomes)...
December 26, 2017: Blood Advances
https://www.readbyqxmd.com/read/29220122/expression-profile-analysis-of-long-non-coding-rna-in-acute-myeloid-leukemia-by-microarray-and-bioinformatics
#9
Yuandong Feng, Ying Shen, Hongli Chen, Xiaman Wang, Ru Zhang, Yue Peng, Xiaoru Lei, Tian Liu, Jing Liu, Liufang Gu, Fangxia Wang, Yun Yang, Ju Bai, Jianli Wang, Wanhong Zhao, Aili He
Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nt that are involved in tumorigenesis and play a key role in cancer progression. To determine whether lncRNAs are involved in acute myeloid leukemia (AML), we analyzed the expression profile of lncRNAs and mRNAs in AML. Five pairs of AML patients and iron deficiency anemia (IDA) controls were screened by microarray. Through coexpression analysis, differently expressed transcripts were divided into modules, and lncRNAs were functionally annotated...
February 2018: Cancer Science
https://www.readbyqxmd.com/read/29185460/reprogramming-to-pluripotency-does-not-require-transition-through-a-primitive-streak-like-state
#10
Stefanie Raab, Moritz Klingenstein, Anna Möller, Anett Illing, Jelena Tosic, Markus Breunig, Georg Kuales, Leonhard Linta, Thomas Seufferlein, Sebastian J Arnold, Alexander Kleger, Stefan Liebau
Pluripotency can be induced in vitro from adult somatic mammalian cells by enforced expression of defined transcription factors regulating and initiating the pluripotency network. Despite the substantial advances over the last decade to improve the efficiency of direct reprogramming, exact mechanisms underlying the conversion into the pluripotent stem cell state are still vaguely understood. Several studies suggested that induced pluripotency follows reversed embryonic development. For somatic cells of mesodermal and endodermal origin that would require the transition through a Primitive streak-like state, which would necessarily require an Eomesodermin (Eomes) expressing intermediate...
November 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29180433/a-stat3-dependent-transcriptional-circuitry-inhibits-cytotoxic-gene-expression-in-t-cells
#11
Thomas Ciucci, Melanie S Vacchio, Rémy Bosselut
CD8+ T cells are preprogrammed for cytotoxic differentiation in the thymus as they acquire expression of the transcription factor Runx3. However, a subset of effector CD8+ T cells (Tc17) produce IL-17 and fail to express cytotoxic genes. Here, we show that the transcription factors directing IL-17 production, STAT3 and RORγt, inhibit cytotoxicity despite persistent Runx3 expression. Cytotoxic gene repression did not require the transcription factor Thpok, which in CD4+ T cells restrains Runx3 functions and cytotoxicity; and STAT3 restrained cytotoxic gene expression in CD8+ T cells responding to viral infection in vivo...
December 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29139478/trigger-happy-resident-memory-cd4-t-cells-inhabit-the-human-lungs
#12
A E Oja, B Piet, C Helbig, R Stark, D van der Zwan, H Blaauwgeers, E B M Remmerswaal, D Amsen, R E Jonkers, P D Moerland, M A Nolte, R A W van Lier, P Hombrink
Resident memory T cells (TRM) reside in the lung epithelium and mediate protective immunity against respiratory pathogens. Although lung CD8+ TRM have been extensively characterized, the properties of CD4+ TRM remain unclear. Here we determined the transcriptional signature of CD4+ TRM, identified by the expression of CD103, retrieved from human lung resection material. Various tissue homing molecules were specifically upregulated on CD4+ TRM, whereas expression of tissue egress and lymph node homing molecules were low...
November 15, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29139476/detection-of-hiv-1-specific-gastrointestinal-tissue-resident-cd8-t-cells-in-chronic-infection
#13
Brenna E Kiniry, Shengbin Li, Anupama Ganesh, Peter W Hunt, Ma Somsouk, Pamela J Skinner, Steven G Deeks, Barbara L Shacklett
Tissue-resident memory (TRM ) CD8+ T-cells are non-recirculating, long-lived cells housed in tissues that can confer protection against mucosal pathogens. Human immunodeficiency virus-1 (HIV-1) is a mucosal pathogen and the gastrointestinal tract is an important site of viral pathogenesis and transmission. Thus, CD8+ TRM cells may be an important effector subset for controlling HIV-1 in mucosal tissues. This study sought to determine the abundance, phenotype, and functionality of CD8+ TRM cells in the context of chronic HIV-1 infection...
November 15, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29091993/germline-competency-of-human-embryonic-stem-cells-depends-on-eomesodermin
#14
Di Chen, Wanlu Liu, Anastasia Lukianchikov, Grace V Hancock, Jill Zimmerman, Matthew G Lowe, Rachel Kim, Zoran Galic, Naoko Irie, M Azim Surani, Steven E Jacobsen, Amander T Clark
In humans, germline competency and the specification of primordial germ cells (PGCs) are thought to occur in a restricted developmental window during early embryogenesis. Despite the importance of specifying the appropriate number of PGCs for human reproduction, the molecular mechanisms governing PGC formation remain largely unexplored. Here, we compared PGC-like cell (PGCLC) differentiation from 18 independently derived human embryonic stem cell (hESC) lines, and discovered that the expression of primitive streak genes were positively associated with hESC germline competency...
January 1, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28966617/peripheral-autoimmune-regulator-induces-exhaustion-of-cd4-and-cd8-effector-t-cells-to-attenuate-autoimmune-diabetes-in-non-obese-diabetic-mice
#15
Divakar Kulshrestha, Li-Tzu Yeh, Ming-Wei Chien, Feng-Cheng Chou, Huey-Kang Sytwu
Autoimmune regulator (Aire) is one of the most crucial genes expressed in the thymus, where it orchestrates the promiscuous expression and presentation of tissue-specific antigens during thymocyte selection. The presence of Aire-expressing cells outside the thymus points toward its plausible extrathymic functions; however, the relative contribution of Aire-expressing cells of hematopoietic origin and their role in the modulation of autoimmune diseases are still obscure. Here, we report that non-obese diabetic mice with transgenic Aire expression under the control of the CD11c (integrin alpha X) promoter were significantly protected from autoimmune diabetes compared with their non-transgenic littermates...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28924369/il-12-influence-mtor-to-modulate-cd8-t-cells-differentiation-through-t-bet-and-eomesodermin-in-response-to-invasive-pulmonary-aspergillosis
#16
Hao Wang, Jingdong Li, Qiyang Han, Fei Yang, Yu Xiao, Meng Xiao, Yingchun Xu, Longxiang Su, Na Cui, Dawei Liu
Objective: To investigate whether mTOR signaling pathway regulate the proliferation and differentiation of CD8(+) T cells by transcription factors T-bet and Eomes, and explore the role of IL-12 in this biological procedure. Methods: Aspergillus fumigatus spore suspension nasal inhalation was used to establish the invasive pulmonary aspergillosis (IPA) mouse model. After inoculation, rapamycin (2mg/kg) each day or IL-12 (5ug/kg) every other day was given for 7 days. The blood samples were obtained before the mice sacrificed and lung specimens were taken...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28855309/il-21-receptor-signaling-is-essential-for-optimal-cd4-t-cell-function-and-control-of-mycobacterium-tuberculosis-infection-in-mice
#17
Satyanarayana Swamy Cheekatla, Deepak Tripathi, Sambasivan Venkatasubramanian, Padmaja Paidipally, Elwyn Welch, Amy R Tvinnereim, Roza Nurieva, Ramakrishna Vankayalapati
In this study, we determined the role of IL-21R signaling in Mycobacterium tuberculosis infection, using IL-21R knockout (KO) mice. A total of 50% of M. tuberculosis H37Rv-infected IL-21R KO mice died in 6 mo compared with no deaths in infected wild type (WT) mice. M. tuberculosis-infected IL-21R KO mice had enhanced bacterial burden and reduced infiltration of Ag-specific T cells in lungs compared with M. tuberculosis-infected WT mice. Ag-specific T cells from the lungs of M. tuberculosis-infected IL-21R KO mice had increased expression of T cell inhibitory receptors, reduced expression of chemokine receptors, proliferated less, and produced less IFN- γ, compared with Ag-specific T cells from the lungs of M...
October 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28790368/signs-of-innate-immune-activation-and-premature-immunosenescence-in-psoriasis-patients
#18
Liisi Šahmatova, Elena Sügis, Marina Šunina, Helen Hermann, Ele Prans, Maire Pihlap, Kristi Abram, Ana Rebane, Hedi Peterson, Pärt Peterson, Külli Kingo, Kai Kisand
Psoriasis is a chronic inflammatory disease that affects skin and is associated with systemic inflammation and many serious comorbidities ranging from metabolic syndrome to cancer. Important discoveries about psoriasis pathogenesis have enabled the development of effective biological treatments blocking the T helper 17 pathway. However, it has not been settled whether psoriasis is a T cell-mediated autoimmune disease or an autoinflammatory disorder that is driven by exaggerated innate immune signalling. Our comparative gene expression and hierarchical cluster analysis reveal important gene circuits involving innate receptors...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28766905/evidence-for-reduced-neurogenesis-in-the-aging-human-hippocampus-despite-stable-stem-cell-markers
#19
Kathryn J Mathews, Katherine M Allen, Danny Boerrigter, Helen Ball, Cynthia Shannon Weickert, Kay L Double
Reduced neurogenesis in the aging mammalian hippocampus has been linked to cognitive deficits and increased risk of dementia. We utilized postmortem human hippocampal tissue from 26 subjects aged 18-88 years to investigate changes in expression of six genes representing different stages of neurogenesis across the healthy adult lifespan. Progressive and significant decreases in mRNA levels of the proliferation marker Ki67 (MKI67) and the immature neuronal marker doublecortin (DCX) were found in the healthy human hippocampus over the lifespan...
October 2017: Aging Cell
https://www.readbyqxmd.com/read/28747319/frontline-science-a-hyporesponsive-subset-of-rat-nk-cells-negative-for-ly49s3-and-nkr-p1b-are-precursors-to-the-functionally-mature-nkr-p1b-subset
#20
Amanda Sudworth, John T Vaage, Marit Inngjerdingen, Lise Kveberg
Rat NK cells are divided into major subsets expressing either Ly49 receptors or the inhibitory NKR-P1B receptor in conjunction with NKG2A/C/E receptors. A minor subset of NKp46+ cells lacking expression of both Ly49 receptors and NKR-P1B is present in blood and spleen and is associated with decreased functional competence. We hypothesized that this subset may represent precursors to Ly49+ and/or NKR-P1B+ NK cells. When cultured in vitro in IL-2 and IL-15 or adoptively transferred to syngeneic hosts, a portion of NKR-P1B- Ly49s3- cells transformed to express NKR-P1B, but very little Ly49s3...
December 2017: Journal of Leukocyte Biology
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