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https://www.readbyqxmd.com/read/28396661/phenotype-of-nk-like-cd8-t-cells-with-innate-features-in-humans-and-their-relevance-in-cancer-diseases
#1
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
#2
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...
April 6, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28289707/eomesodermin-and-t-bet-mark-developmentally-distinct-human-natural-killer-cells
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
https://www.readbyqxmd.com/read/27827375/predominance-of-weakly-cytotoxic-t-bet-low-eomes-neg-cd8-t-cells-in-human-gastrointestinal-mucosa-implications-for-hiv-infection
#9
B E Kiniry, A Ganesh, J W Critchfield, P W Hunt, F M Hecht, M Somsouk, S G Deeks, B L Shacklett
The gastrointestinal mucosa is an important site of HIV acquisition, viral replication, and pathogenesis. Immune cells in mucosal tissues frequently differ in phenotype and function from their non-mucosal counterparts. Although perforin-mediated cytotoxicity as measured in blood is a recognized correlate of HIV immune control, its role in gastrointestinal tissues is unknown. We sought to elucidate the cytotoxic features of rectal mucosal CD8(+) T-cells in HIV infected and uninfected subjects. Perforin expression and lytic capacity were significantly reduced in rectal CD8(+) T-cells compared with their blood counterparts, regardless of HIV clinical status; granzyme B (GrzB) was reduced to a lesser extent...
November 9, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/27790219/transcription-factor-bcl11b-controls-effector-and-memory-cd8-t-cell-fate-decision-and-function-during-poxvirus-infection
#10
Georges Abboud, Jessica Stanfield, Vikas Tahiliani, Pritesh Desai, Tarun E Hutchinson, Kyle J Lorentsen, Jonathan J Cho, Dorina Avram, Shahram Salek-Ardakani
CD8(+) T cells play an important role in host resistance to many viral infections, but the underlying transcriptional mechanisms governing their differentiation and functionality remain poorly defined. By using a highly virulent systemic and respiratory poxvirus infection in mice, we show that the transcription factor Bcl11b provides a dual trigger that sustains the clonal expansion of virus-specific effector CD8(+) T cells, while simultaneously suppressing the expression of surface markers associated with short-lived effector cell (SLEC) differentiation...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27599295/tgf-%C3%AE-receptor-maintains-cd4-t-helper-cell-identity-during-chronic-viral-infections
#11
Gavin M Lewis, Ellen J Wehrens, Lara Labarta-Bajo, Hendrik Streeck, Elina I Zuniga
Suppression of CD8 and CD4 T cells is a hallmark in chronic viral infections, including hepatitis C and HIV. While multiple pathways are known to inhibit CD8 T cells, the host molecules that restrict CD4 T cell responses are less understood. Here, we used inducible and CD4 T cell-specific deletion of the gene encoding the TGF-β receptor during chronic lymphocytic choriomeningitis virus infection in mice, and determined that TGF-β signaling restricted proliferation and terminal differentiation of antiviral CD4 T cells...
October 3, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27539959/reciprocal-regulation-of-bmf-and-birc5-survivin-linked-to-eomes-overexpression-in-colorectal-cancer
#12
Rong Wang, Yuki Kang, Christiane V Löhr, Kay A Fischer, C Samuel Bradford, Gavin Johnson, Wan Mohaiza Dashwood, David E Williams, Emily Ho, Roderick H Dashwood
Eomesodermin (Eomes) is a T-box transcription factor that has been implicated in the etiology of colorectal cancer and other human malignancies. We screened a panel of human primary colon cancers and patient-matched controls (n = 30) and detected Eomes overexpression at the mRNA and protein level. Similar results were obtained in a panel of rat colon tumors and adjacent normal-looking colonic mucosa (n = 24). In human colon cancer cells, forced overexpression of Eomes enhanced cell viability and protected against staurosporine-induced apoptosis...
October 28, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27486665/temporal-dynamics-of-cd8-t-cell-effector-responses-during-primary-hiv-infection
#13
Korey R Demers, George Makedonas, Marcus Buggert, Michael A Eller, Sarah J Ratcliffe, Nilu Goonetilleke, Chris K Li, Leigh Anne Eller, Kathleen Rono, Lucas Maganga, Sorachai Nitayaphan, Hannah Kibuuka, Jean-Pierre Routy, Mark K Slifka, Barton F Haynes, Andrew J McMichael, Nicole F Bernard, Merlin L Robb, Michael R Betts
The loss of HIV-specific CD8+ T cell cytolytic function is a primary factor underlying progressive HIV infection, but whether HIV-specific CD8+ T cells initially possess cytolytic effector capacity, and when and why this may be lost during infection, is unclear. Here, we assessed CD8+ T cell functional evolution from primary to chronic HIV infection. We observed a profound expansion of perforin+ CD8+ T cells immediately following HIV infection that quickly waned after acute viremia resolution. Selective expression of the effector-associated transcription factors T-bet and eomesodermin in cytokine-producing HIV-specific CD8+ T cells differentiated HIV-specific from bulk memory CD8+ T cell effector expansion...
August 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27425607/molecular-mechanisms-regulating-t-helper-1-versus-t-follicular-helper-cell-differentiation-in-humans
#14
Nathalie Schmitt, Yang Liu, Salah-Eddine Bentebibel, Hideki Ueno
IL-12 is important for the differentiation of T follicular helper (Tfh) cells, as well as Th1 cells in humans. Still, how IL-12 signals regulate Tfh versus Th1 cell differentiation remains poorly characterized. Here we aimed to determine the molecular mechanisms that regulate the differentiation and the function of IL-12-stimulated human naive CD4(+) T cells. We found that T-bet promoted the expression of CXCR5 in human CD4(+) T cells. We provide evidence that T-bet does not strongly inhibit the Tfh cell differentiation program per se but diminishes the functions to provide help to B cells...
July 26, 2016: Cell Reports
https://www.readbyqxmd.com/read/27411458/mtor-modulates-lymphocyte-differentiation-through-t-bet-and-eomesodermin-in-response-to-invasive-pulmonary-aspergillosis-in-rats
#15
Na Cui, Long-Xiang Su, Hao Wang, Meng Xiao, Fei Yang, Min Zheng, Xin Li, Ying-Chun Xu, Da-Wei Liu
BACKGROUND: Aspergillosis infection is common in the patients with insufficient immunity. The role of mammalian target of rapamycin (mTOR), T-box expressed in T-cells (T-bet), and eomesodermin (EOMES) in mediating T lymphocytes differentiation in response to Aspergillus fumigatus infection in immunocompromised rats was investigated in this study. METHODS: Invasive pulmonary aspergillosis (IPA) of immunosuppressive twenty male rats were established and sacrificed at 24 h (n = 5), 48 h (n = 5), 72 h (n = 5), and 96 h (n = 5) after A...
July 20, 2016: Chinese Medical Journal
https://www.readbyqxmd.com/read/27394699/diversity-and-function-of-group-1-innate-lymphoid-cells
#16
Victor Cortez, Marco Colonna
Innate lymphoid cells (ILCs) are a heterogeneous population of cells with diverse roles in immune responses. Three major groups of ILCs have been defined on the basis of similarity in their production of signature cytokines, developmental requirements, and phenotypic markers. Group 1 ILCs produce IFN-γ, express the T-box transcription factors (TF) Eomesodermin (Eomes) and/or T-bet. Group 2 ILCs secrete IL-5 and IL-13, express the TF GATA-3, and are identified by the expression of KLRG1, the receptor IL-7 (IL7R, also known as CD127), and the receptor for IL-33 (IL33R)...
July 6, 2016: Immunology Letters
https://www.readbyqxmd.com/read/27379101/t-bet-and-eomesodermin-in-nk-cell-development-maturation-and-function
#17
REVIEW
Federico Simonetta, Amandine Pradier, Eddy Roosnek
Recent reports give insights into the role of the T-box transcription factors, T-bet and Eomesodermin (Eomes), in NK cell biology. In this mini-review, we recapitulate the initial reports that delineate T-bet and Eomes as master regulators of NK cell development, maturation, and function. We discuss how T-bet and Eomes expression is regulated during NK cell development and peripheral maturation. Furthermore, we summarize the current literature on the role of T-bet and Eomes in the transcriptional regulation of NK cell function and review possible effects of T-box transcription factor anomalies during aging, infection, cancer, and after hematopoietic stem cell transplantation...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27324129/osteoclast-primed-foxp3-cd8-t-cells-induce-t-bet-eomesodermin-and-ifn-%C3%AE-to-regulate-bone-resorption
#18
Elena V Shashkova, Jahnavi Trivedi, Anna B Cline-Smith, Chloe Ferris, Zachary S Buchwald, Jesse Gibbs, Deborah Novack, Rajeev Aurora
Osteoimmunology arose from the recognition that cytokines produced by lymphocytes can affect bone homeostasis. We have previously shown that osteoclasts, cells that resorb bone, act as APCs. Cross-presentation of Ags by osteoclasts leads to expression of CD25 and Foxp3, markers of regulatory T cells in the CD8 T cells. Octeoclast-induced Foxp3(+) CD25(+) regulatory CD8 T cells (OC-iTcREG) suppress priming of CD4 and CD8 T cells by dendritic cells. OC-iTcREG also limit bone resorption by osteoclasts, forming a negative feedback loop...
August 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27298446/il-4-sensitivity-shapes-the-peripheral-cd8-t-cell-pool-and-response-to-infection
#19
Kristin R Renkema, June-Yong Lee, You Jeong Lee, Sara E Hamilton, Kristin A Hogquist, Stephen C Jameson
Previous studies have revealed that a population of innate memory CD8(+) T cells is generated in response to IL-4, first appearing in the thymus and bearing high expression levels of Eomesodermin (Eomes) but not T-bet. However, the antigen specificity and functional properties of these cells is poorly defined. In this study, we show that IL-4 regulates not only the frequency and function of innate memory CD8(+) T cells, but also regulates Eomes expression levels and functional reactivity of naive CD8(+) T cells...
June 27, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27212596/pathological-mechanism-of-secondary-progressive-multiples-sclerosis-and-its-animal-model
#20
REVIEW
Shinji Oki
  Development of acute experimental autoimmune encephalomyelitis (EAE) depends on Th17 cells expressing the nuclear factor NR4A2, which we have previously reported to be upregulated in peripheral blood T cells from patients of multiple sclerosis (MS). EAE induced in mice lacking NR4A2 in T cells showed a great reduction in Th17-mediated acute symptoms, whereas a late-onset disease independent of NR4A2 was still inducible. We identified cytotoxic T-cell-like CD4+ T cells expressing the T-box transcription factor Eomesodermin (Eomes) as a pathogenic component for the development of the late-onset disease...
2016: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
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