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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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...
July 26, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28738016/eomesodermin-promotes-the-development-of-type-1-regulatory-t-tr1-cells
#7
Ping Zhang, Jason S Lee, Kate H Gartlan, Iona S Schuster, Iain Comerford, Antiopi Varelias, Md Ashik Ullah, Slavica Vuckovic, Motoko Koyama, Rachel D Kuns, Kelly R Locke, Kirrilee J Beckett, Stuart D Olver, Luke D Samson, Marcela Montes de Oca, Fabian de Labastida Rivera, Andrew D Clouston, Gabrielle T Belz, Bruce R Blazar, Kelli P MacDonald, Shaun R McColl, Ranjeny Thomas, Christian R Engwerda, Mariapia A Degli-Esposti, Axel Kallies, Siok-Keen Tey, Geoffrey R Hill
Type 1 regulatory T (TR1) cells are Foxp3(-) interleukin-10 (IL-10)-producing CD4(+) T cells with potent immunosuppressive properties, but their requirements for lineage development have remained elusive. We show that TR1 cells constitute the most abundant regulatory population after allogeneic bone marrow transplantation (BMT), express the transcription factor Eomesodermin (Eomes), and are critical for the prevention of graft-versus-host disease. We demonstrate that Eomes is required for TR1 cell differentiation, during which it acts in concert with the transcription factor B lymphocyte-induced maturation protein-1 (Blimp-1) by transcriptionally activating IL-10 expression and repressing differentiation into other T helper cell lineages...
April 7, 2017: Science Immunology
https://www.readbyqxmd.com/read/28737488/modulation-of-let-7-mirnas-controls-the-differentiation-of-effector-cd8-t-cells
#8
Alexandria C Wells, Keith A Daniels, Constance C Angelou, Eric Fagerberg, Amy S Burnside, Michele Markstein, Dominique Alfandari, Raymond M Welsh, Elena L Pobezinskaya, Leonid A Pobezinsky
The differentiation of naive CD8 T cells into effector cytotoxic T lymphocytes upon antigen stimulation is necessary for successful antiviral, and antitumor immune responses. Here, using a mouse model, we describe a dual role for the let-7 microRNAs in the regulation of CD8 T cell responses, where maintenance of the naive phenotype in CD8 T cells requires high levels of let-7 expression, while generation of cytotoxic T lymphocytes depends upon T cell receptor-mediated let-7 downregulation. Decrease of let-7 expression in activated T cells enhances clonal expansion and the acquisition of effector function through derepression of the let-7 targets, including Myc and Eomesodermin...
July 24, 2017: ELife
https://www.readbyqxmd.com/read/28684164/neem-leaf-glycoprotein-generates-superior-tumor-specific-central-memory-cd8-t-cells-than-cyclophosphamide-that-averts-post-surgery-solid-sarcoma-recurrence
#9
Sarbari Ghosh, Madhurima Sarkar, Tithi Ghosh, Ipsita Guha, Avishek Bhuniya, Akata Saha, Shayani Dasgupta, Subhasis Barik, Anamika Bose, Rathindranath Baral
The success of cancer vaccines is limited as most of them induce corrupted CD8(+) T cell memory populations. We reported earlier that a natural immunomodulator, neem leaf glycoprotein (NLGP), therapeutically restricts tumor growth in a CD8(+) T cell-dependent manner. Here, our objective is to study whether memory CD8(+) T cell population is generated in sarcoma hosts after therapeutic NLGP treatment and their role in prevention of post-surgery tumor recurrence, in comparison to the immunostimulatory metronomic cyclophosphamide (CTX) treatment...
July 3, 2017: Vaccine
https://www.readbyqxmd.com/read/28630305/multiple-layers-of-heterogeneity-and-subset-diversity-in-human-mait-cell-responses-to-distinct-microorganisms-and-to-innate-cytokines
#10
Joana Dias, Edwin Leeansyah, Johan K Sandberg
Mucosa-associated invariant T (MAIT) cells are a large innate-like T-cell subset in humans defined by invariant TCR Vα7.2 use and expression of CD161. MAIT cells recognize microbial riboflavin metabolites of bacterial or fungal origin presented by the monomorphic MR1 molecule. The extraordinary level of evolutionary conservation of MR1 and the limited known diversity of riboflavin metabolite antigens have suggested that MAIT cells are relatively homogeneous and uniform in responses against diverse microbes carrying the riboflavin biosynthesis pathway...
July 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28550044/t-cells-lacking-hdac11-have-increased-effector-functions-and-mediate-enhanced-alloreactivity-in-a-murine-model
#11
David M Woods, Karrune V Woan, Fengdong Cheng, Andressa L Sodré, Dapeng Wang, Yongxia Wu, Zi Wang, Jie Chen, John Powers, Javier Pinilla-Ibarz, Yu Yu, Ya Zhang, Xuefeng Wu, Xiaoyan Zheng, Jeffrey Weber, Wayne W Hancock, Edward Seto, Alejandro Villagra, Xue-Zhong Yu, Eduardo M Sotomayor
Histone acetylation and the families of enzymes responsible for controlling these epigenetic marks have been implicated in regulating T-cell maturation and phenotype. Here, we demonstrate a previously undefined role of histone deacetylase 11 (HDAC11) in regulating T-cell effector functions. Using EGFP-HDAC11 transgenic reporter mice, we found that HDAC11 expression was lower in effector relative to naive and central memory T-cell populations, and activation of resting T cells resulted in its decreased expression...
July 13, 2017: Blood
https://www.readbyqxmd.com/read/28485322/role-of-triggering-receptor-expressed-on-myeloid-cell-1-expression-in-mammalian-target-of-rapamycin-modulation-of-cd8-t-cell-differentiation-during-the-immune-response-to-invasive-pulmonary-aspergillosis
#12
Na Cui, Hao Wang, Long-Xiang Su, Jia-Hui Zhang, Yun Long, Da-Wei Liu
BACKGROUND: Triggering receptor expressed on myeloid cell-1 (TREM-1) may play a vital role in mammalian target of rapamycin (mTOR) modulation of CD8+ T-cell differentiation through the transcription factors T-box expressed in T-cells and eomesodermin during the immune response to invasive pulmonary aspergillosis (IPA). This study aimed to investigate whether the mTOR signaling pathway modulates the proliferation and differentiation of CD8+ T-cells during the immune response to IPA and the role TREM-1 plays in this process...
May 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28396661/phenotype-of-nk-like-cd8-t-cells-with-innate-features-in-humans-and-their-relevance-in-cancer-diseases
#13
Alice Barbarin, Emilie Cayssials, Florence Jacomet, Nicolas Gonzalo Nunez, Sara Basbous, Lucie Lefèvre, Myriam Abdallah, Nathalie Piccirilli, Benjamin Morin, Vincent Lavoue, Véronique Catros, Eliane Piaggio, André Herbelin, Jean-Marc Gombert
Unconventional T cells are defined by their capacity to respond to signals other than the well-known complex of peptides and major histocompatibility complex proteins. Among the burgeoning family of unconventional T cells, innate-like CD8(+) T cells in the mouse were discovered in the early 2000s. This subset of CD8(+) T cells bears a memory phenotype without having encountered a foreign antigen and can respond to innate-like IL-12 + IL-18 stimulation. Although the concept of innate memory CD8(+) T cells is now well established in mice, whether an equivalent memory NK-like T-cell population exists in humans remains under debate...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28386934/eomes-expression-reports-the-progressive-differentiation-of-ifn-%C3%AE-producing-th1-like-%C3%AE-%C3%AE-t%C3%A2-cells
#14
Ciro N R Lino, Joana Barros-Martins, Linda Oberdörfer, Thierry Walzer, Immo Prinz
The transcription factor Eomesodermin (Eomes) plays a crucial role in regulating cytotoxic function, development, and survival of immune cells. γδ T cells can express Eomes, but its contribution to their differentiation is unknown. Using Eomes-IRES-GFP mice, we show that Eomes(+) γδ T cells are unequally distributed among organs, with the highest proportion in spleen. While the majority of Eomes(+) γδ T cells expressed Vγ1(+) and Vγ4(+) TCRs, Eomes was absent in Vγ5(+) , Vγ6(+) , and Vγ7(+) subsets...
June 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28289707/eomesodermin-and-t-bet-mark-developmentally-distinct-human-natural-killer-cells
#15
Amélie Collins, Nyanza Rothman, Kang Liu, Steven L Reiner
Immaturity of the immune system of human fetuses and neonates is often invoked to explain their increased susceptibility to infection; however, the development of the fetal innate immune system in early life remains incompletely explored. We now show that the most mature NK cells found in adult (or postnatal) human circulation (CD94(-)CD16(+)) are absent during ontogeny. Human fetal NK cells were found to express the 2 signature T-box transcription factors essential for the development of all murine NK and NK-like cells, eomesodermin (Eomes) and T-bet...
March 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28280496/cd4-ctl-a-cytotoxic-subset-of-cd4-t-cells-their-differentiation-and-function
#16
REVIEW
Arata Takeuchi, Takashi Saito
CD4(+) T cells with cytotoxic activity (CD4 CTL) have been observed in various immune responses. These cells are characterized by their ability to secrete granzyme B and perforin and to kill the target cells in an MHC class II-restricted fashion. Although CD4 CTLs were once thought to be an in vitro artifact associated with long-term culturing, they have since been identified in vivo and shown to play important roles in antiviral and antitumor immunity, as well as in inflammation. Functional characterization of CD4 CTL suggests their potential significance for therapeutic purposes...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28193872/nf%C3%AE%C2%BAb-pim-1-eomesodermin-axis-is-critical-for-maintaining-cd8-t-cell-memory-quality
#17
Karin M Knudson, Curtis J Pritzl, Vikas Saxena, Amnon Altman, Mark A Daniels, Emma Teixeiro
T-cell memory is critical for long-term immunity. However, the factors involved in maintaining the persistence, function, and phenotype of the memory pool are undefined. Eomesodermin (Eomes) is required for the establishment of the memory pool. Here, we show that in T cells transitioning to memory, the expression of high levels of Eomes is not constitutive but rather requires a continuum of cell-intrinsic NFκB signaling. Failure to maintain NFκB signals after the peak of the response led to impaired Eomes expression and a defect in the maintenance of CD8 T-cell memory...
February 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28137869/akt-signaling-is-critical-for-memory-cd8-t-cell-development-and-tumor-immune-surveillance
#18
Anne Rogel, Jane E Willoughby, Sarah L Buchan, Henry J Leonard, Stephen M Thirdborough, Aymen Al-Shamkhani
Memory CD8(+) T cells confer long-term immunity against tumors, and anticancer vaccines therefore should maximize their generation. Multiple memory CD8(+) T-cell subsets with distinct functional and homing characteristics exist, but the signaling pathways that regulate their development are ill defined. Here we examined the role of the serine/threonine kinase Akt in the generation of protective immunity by CD8(+) T cells. Akt is known to be activated by the T-cell antigen receptor and the cytokine IL-2, but its role in T-cell immunity in vivo has not been explored...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28057273/eomesodermin-at-dawn-of-cell-fate-decisions-during-early-embryogenesis
#19
REVIEW
S Probst, S J Arnold
Proteins of the large family of T-box transcription factors are implicated in a broad spectrum of developmental processes. Loss-of-function mutations of T-box(Tbx) factors frequently cause severe embryonic phenotypes, often resulting from defects in cell fate specification and lineage differentiation. This review summarizes current knowledge on the functions of the T-box transcription factor Eomesodermin (Eomes) from postfertilization development until gastrulation stages of vertebrate embryos. Eomes exhibits evolutionary conserved functions in cell lineage specification and morphogenesis during gastrulation in all studied vertebrate model systems...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28052005/bortezomib-augments-lymphocyte-stimulatory-cytokine-signaling-in-the-tumor-microenvironment-to-sustain-cd8-t-cell-antitumor-function
#20
Samuel T Pellom, Duafalia F Dudimah, Menaka C Thounaojam, Roman V Uzhachenko, Ashutosh Singhal, Ann Richmond, Anil Shanker
Tumor-induced immune tolerance poses a major challenge for therapeutic interventions aimed to manage cancer. We explored approaches to overcome T-cell suppression in murine breast and kidney adenocarcinomas, and lung fibrosarcoma expressing immunogenic antigens. We observed that treatment with a reversible proteasome inhibitor bortezomib (1 mg/kg body weight) in tumor-bearing mice significantly enhanced the expression of lymphocyte-stimulatory cytokines IL-2, IL-12, and IL-15. Notably, bortezomib administration reduced pulmonary nodules of mammary adenocarcinoma 4T1...
January 31, 2017: Oncotarget
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