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  1. AU="Robin Kageyama"
  2. AU="Thapa Shrestha, Upendra"
  3. AU="Litvinovskaya, Raisa P"
  4. AU="MacDougall‐Shackleton, Elizabeth A."
  5. AU="Rajendram, Rathie"
  6. AU=Laxminarayan Ramanan
  7. AU="Perriman, Diana M"
  8. AU=Radich Jerald P
  9. AU="Velthuis, Birgitta"
  10. AU="Gibbs, Tom"
  11. AU=Mezzabotta Federica
  12. AU="Jalas, Sören"
  13. AU="Suma, Rache"
  14. AU="Calderón, Alejandro"
  15. AU="Demertzi, Vasiliki"
  16. AU="Leonidov, A"
  17. AU="Luo, Suxin"
  18. AU="Thompson, Charlotte A S"
  19. AU="Dubbel, Polly"
  20. AU="Ten Bosch, Nora"
  21. AU="Giménez-Arnau, Ana Maria"
  22. AU=Maul Robert W.
  23. AU="Ivn Prez-MaldonadoauthorLaboratorio de Toxicologa Molecular, Centro de Investigacin Aplicada en Ambiente y Salud (CIAAS), Coordinacin para la Innovacin y Aplicacin de la Ciencia y la Tecnologa (CIACYT), Universidad Autnoma de San Luis Potos, MexicoFacultad de Medicina, Universidad Autnoma de San Luis Potos, San Luis Potos, MexicoFacultad de Enfermera, Universidad Autnoma de Zacatecas, Mexico"
  24. AU="Hansen, Kristian Schultz"
  25. AU="Davenport, Bennett"

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  1. Artikel ; Online: Selective Export into Extracellular Vesicles and Function of tRNA Fragments during T Cell Activation

    Ni-Ting Chiou / Robin Kageyama / K. Mark Ansel

    Cell Reports, Vol 25, Iss 12, Pp 3356-3370.e

    2018  Band 4

    Abstract: Summary: The discovery of microRNA (miRNA) sorting into extracellular vesicles (EVs) revealed a novel mode of intercellular communication and uncovered a link between cellular endomembrane compartments and small RNAs in EV-secreting cells. Using a two- ... ...

    Abstract Summary: The discovery of microRNA (miRNA) sorting into extracellular vesicles (EVs) revealed a novel mode of intercellular communication and uncovered a link between cellular endomembrane compartments and small RNAs in EV-secreting cells. Using a two-step ultracentrifugation procedure to isolate EVs released by T cells, we found that 45% of tRNA fragments (tRFs), but fewer than 1% of miRNAs, were significantly enriched in EVs compared with the corresponding cellular RNA. T cell activation induced the EV-mediated release of a specific set of tRFs derived from the 5′ end and 3′-internal region of tRNAs without variable loops. Inhibition of EV biogenesis pathways specifically led to the accumulation of these activation-induced EV-enriched tRFs within multivesicular bodies (MVBs). Introducing antisense oligonucleotides to inhibit these tRFs enhanced T cell activation. Taken together, these results demonstrate that T cells selectively release tRFs into EVs via MVBs and suggest that this process may remove tRFs that repress immune activation. : Chiou et al. show that T cells release extracellular vesicles that carry RNA cargo enriched in tRNA fragments. Immune activating signals enhance multivesicular body formation and the secretion of vesicles containing specific tRNA fragments. Within cells, these tRNA fragments inhibit T cell activation and cytokine production. Keywords: tRNA fragment, tsRNA, extracellular vesicle, exosome, T lymphocyte
    Schlagwörter Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 500
    Sprache Englisch
    Erscheinungsdatum 2018-12-01T00:00:00Z
    Verlag Elsevier
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  2. Artikel ; Online: GCLiPP

    Wandi S. Zhu / Adam J. Litterman / Harshaan S. Sekhon / Robin Kageyama / Maya M. Arce / Kimberly E. Taylor / Wenxue Zhao / Lindsey A. Criswell / Noah Zaitlen / David J. Erle / K. Mark Ansel

    Genome Biology, Vol 24, Iss 1, Pp 1-

    global crosslinking and protein purification method for constructing high-resolution occupancy maps for RNA binding proteins

    2023  Band 30

    Abstract: Abstract GCLiPP is a global RNA interactome capture method that detects RNA-binding protein (RBP) occupancy transcriptome-wide. GCLiPP maps RBP-occupied sites at a higher resolution than phase separation-based techniques. GCLiPP sequence tags correspond ... ...

    Abstract Abstract GCLiPP is a global RNA interactome capture method that detects RNA-binding protein (RBP) occupancy transcriptome-wide. GCLiPP maps RBP-occupied sites at a higher resolution than phase separation-based techniques. GCLiPP sequence tags correspond with known RBP binding sites and are enriched for sites detected by RBP-specific crosslinking immunoprecipitation (CLIP) for abundant cytosolic RBPs. Comparison of human Jurkat T cells and mouse primary T cells uncovers shared peaks of GCLiPP signal across homologous regions of human and mouse 3′ UTRs, including a conserved mRNA-destabilizing cis-regulatory element. GCLiPP signal overlapping with immune-related SNPs uncovers stabilizing cis-regulatory regions in CD5, STAT6, and IKZF1.
    Schlagwörter Post-transcriptional regulation ; RNA-binding proteins (RBP) ; T cells ; Cis-regulatory elements ; Biology (General) ; QH301-705.5 ; Genetics ; QH426-470
    Sprache Englisch
    Erscheinungsdatum 2023-12-01T00:00:00Z
    Verlag BMC
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  3. Artikel ; Online: Forced expression of the non-coding RNA miR-17∼92 restores activation and function in CD28-deficient CD4+ T cells

    Marianne Dölz / Marko Hasiuk / John D. Gagnon / Mara Kornete / Romina Marone / Glenn Bantug / Robin Kageyama / Christoph Hess / K. Mark Ansel / Denis Seyres / Julien Roux / Lukas T. Jeker

    iScience, Vol 25, Iss 11, Pp 105372- (2022)

    2022  

    Abstract: Summary: CD28 provides the prototypical costimulatory signal required for productive T-cell activation. Known molecular consequences of CD28 costimulation are mostly based on studies of protein signaling molecules. The microRNA cluster miR-17∼92 is ... ...

    Abstract Summary: CD28 provides the prototypical costimulatory signal required for productive T-cell activation. Known molecular consequences of CD28 costimulation are mostly based on studies of protein signaling molecules. The microRNA cluster miR-17∼92 is induced by T cell receptor stimulation and further enhanced by combined CD28 costimulation. We demonstrate that transgenic miR-17∼92 cell-intrinsically largely overcomes defects caused by CD28 deficiency. Combining genetics, transcriptomics, bioinformatics, and biochemical miRNA:mRNA interaction maps we empirically validate miR-17∼92 target genes that include several negative regulators of T cell activation. CD28-deficient T cells exhibit derepressed miR-17∼92 target genes during activation. CRISPR/Cas9-mediated ablation of the miR-17∼92 targets Pten and Nrbp1 in naive CD28−/− CD4+ T cells differentially increases proliferation and expression of the activation markers CD25 and CD44, respectively. Thus, we propose that miR-17∼92 constitutes a central mediator for T cell activation, integrating signals by the TCR and CD28 costimulation by dampening multiple brakes that prevent T cell activation.
    Schlagwörter Biological sciences ; molecular mechanism of gene regulation ; immunology ; Science ; Q
    Thema/Rubrik (Code) 570
    Sprache Englisch
    Erscheinungsdatum 2022-11-01T00:00:00Z
    Verlag Elsevier
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  4. Artikel ; Online: miR-29 Sustains B Cell Survival and Controls Terminal Differentiation via Regulation of PI3K Signaling

    Marcus J. Hines / Maryaline Coffre / Tenny Mudianto / Marisella Panduro / Eric J. Wigton / Cosmin Tegla / Victoria Osorio-Vasquez / Robin Kageyama / David Benhamou / Oriana Perez / Sofia Bajwa / Michael T. McManus / K. Mark Ansel / Doron Melamed / Sergei B. Koralov

    Cell Reports, Vol 33, Iss 9, Pp 108436- (2020)

    2020  

    Abstract: Summary: The phosphatidylinositol 3-kinase (PI3K) signaling cascade downstream of the B cell receptor (BCR) signalosome is essential for B cell maturation. Proper signaling strength is maintained through the PI3K negative regulator phosphatase and tensin ...

    Abstract Summary: The phosphatidylinositol 3-kinase (PI3K) signaling cascade downstream of the B cell receptor (BCR) signalosome is essential for B cell maturation. Proper signaling strength is maintained through the PI3K negative regulator phosphatase and tensin homolog (PTEN). Although a role for microRNA (miRNA)-dependent control of the PTEN-PI3K axis has been described, the contribution of individual miRNAs to the regulation of this crucial signaling modality in mature B lymphocytes remains to be elucidated. Our analyses reveal that ablation of miR-29 specifically in B lymphocytes results in an increase in PTEN expression and dampening of the PI3K pathway in mature B cells. This dysregulation has a profound impact on the survival of B lymphocytes and results in increased class switch recombination and decreased plasma cell differentiation. Furthermore, we demonstrate that ablation of one copy of Pten is sufficient to ameliorate the phenotypes associated with miR-29 loss. Our data suggest a critical role for the miR-29-PTEN-PI3K regulatory axis in mature B lymphocytes.
    Schlagwörter miR-29 ; B cell ; B lymphocyte ; PI3K ; PTEN ; Plasma Cell ; Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 572
    Sprache Englisch
    Erscheinungsdatum 2020-12-01T00:00:00Z
    Verlag Elsevier
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  5. Artikel ; Online: miR-15/16 Restrain Memory T Cell Differentiation, Cell Cycle, and Survival

    John D. Gagnon / Robin Kageyama / Hesham M. Shehata / Marlys S. Fassett / Darryl J. Mar / Eric J. Wigton / Kristina Johansson / Adam J. Litterman / Pamela Odorizzi / Dimitre Simeonov / Brian J. Laidlaw / Marisella Panduro / Sana Patel / Lukas T. Jeker / Margaret E. Feeney / Michael T. McManus / Alexander Marson / Mehrdad Matloubian / Shomyseh Sanjabi /
    K. Mark Ansel

    Cell Reports, Vol 28, Iss 8, Pp 2169-2181.e

    2019  Band 4

    Abstract: Summary: Coordinate control of T cell proliferation, survival, and differentiation are essential for host protection from pathogens and cancer. Long-lived memory cells, whose precursors are formed during the initial immunological insult, provide ... ...

    Abstract Summary: Coordinate control of T cell proliferation, survival, and differentiation are essential for host protection from pathogens and cancer. Long-lived memory cells, whose precursors are formed during the initial immunological insult, provide protection from future encounters, and their generation is the goal of many vaccination strategies. microRNAs (miRNAs) are key nodes in regulatory networks that shape effective T cell responses through the fine-tuning of thousands of genes. Here, using compound conditional mutant mice to eliminate miR-15/16 family miRNAs in T cells, we show that miR-15/16 restrict T cell cycle, survival, and memory T cell differentiation. High throughput sequencing of RNA isolated by cross-linking immunoprecipitation of AGO2 combined with gene expression analysis in miR-15/16-deficient T cells indicates that these effects are mediated through the direct inhibition of an extensive network of target genes within pathways critical to cell cycle, survival, and memory. : Coordinate control of T cell proliferation, survival, and differentiation are essential for effective cell-mediated adaptive immunity. Gagnon et al. define roles for the miR-15/16 family of microRNAs in restricting T cell cycle and long-lived memory T cell accumulation through the direct inhibition of a very large network of target mRNAs. Keywords: microRNA, miRNA, miR-16, miR-15a, miR-15b, IL-7 receptor, CD127, Argonaute HITS-CLIP, cell cycle, T cell memory
    Schlagwörter Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 571
    Sprache Englisch
    Erscheinungsdatum 2019-08-01T00:00:00Z
    Verlag Elsevier
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  6. Artikel ; Online: IL-21 and IL-6 are critical for different aspects of B cell immunity and redundantly induce optimal follicular helper CD4 T cell (Tfh) differentiation.

    Danelle Eto / Christopher Lao / Daniel DiToro / Burton Barnett / Tania C Escobar / Robin Kageyama / Isharat Yusuf / Shane Crotty

    PLoS ONE, Vol 6, Iss 3, p e

    2011  Band 17739

    Abstract: Cytokines are important modulators of lymphocytes, and both interleukin-21 (IL-21) and IL-6 have proposed roles in T follicular helper (Tfh) differentiation, and directly act on B cells. Here we investigated the absence of IL-6 alone, IL-21 alone, or the ...

    Abstract Cytokines are important modulators of lymphocytes, and both interleukin-21 (IL-21) and IL-6 have proposed roles in T follicular helper (Tfh) differentiation, and directly act on B cells. Here we investigated the absence of IL-6 alone, IL-21 alone, or the combined lack of IL-6 and IL-21 on Tfh differentiation and the development of B cell immunity in vivo. C57BL/6 or IL-21(-/-) mice were treated with a neutralizing monoclonal antibody against IL-6 throughout the course of an acute viral infection (lymphocytic choriomeningitis virus, LCMV). The combined absence of IL-6 and IL-21 resulted in reduced Tfh differentiation and reduced Bcl6 protein expression. In addition, we observed that these cytokines had a large impact on antigen-specific B cell responses. IL-6 and IL-21 collaborate in the acute T-dependent antiviral antibody response (90% loss of circulating antiviral IgG in the absence of both cytokines). In contrast, we observed reduced germinal center formation only in the absence of IL-21. Absence of IL-6 had no impact on germinal centers, and combined absence of both IL-21 and IL-6 revealed no synergistic effect on germinal center B cell development. Studying CD4 T cells in vitro, we found that high IL-21 production was not associated with high Bcl6 or CXCR5 expression. TCR stimulation of purified naïve CD4 T cells in the presence of IL-6 also did not result in Tfh differentiation, as determined by Bcl6 or CXCR5 protein expression. Cumulatively, our data indicates that optimal Tfh formation requires IL-21 and IL-6, and that cytokines alone are insufficient to drive Tfh differentiation.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 570
    Sprache Englisch
    Erscheinungsdatum 2011-03-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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