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  1. Article ; Online: Correction

    Nadia S Kurd / Lydia K Lutes / Jaewon Yoon / Shiao Wei Chan / Ivan L Dzhagalov / Ashley R Hoover / Ellen A Robey

    eLife, Vol

    A role for phagocytosis in inducing cell death during thymocyte negative selection

    2020  Volume 9

    Keywords Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2020-02-01T00:00:00Z
    Publisher eLife Sciences Publications Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Examination of Fas-Induced Apoptosis of Murine Thymocytes in Thymic Tissue Slices Reveals That Fas Is Dispensable for Negative Selection

    Chang-Feng Chu / Hsing-Kai Feng / Kuang-Hui Sun / Chia-Lin Hsu / Ivan L. Dzhagalov

    Frontiers in Cell and Developmental Biology, Vol

    2020  Volume 8

    Abstract: The death receptor Fas can induce cell death through the extrinsic pathway of apoptosis in a variety of cells, including developing thymocytes. Although Fas-induced cell death has been researched and modeled extensively, most of the studies have been ... ...

    Abstract The death receptor Fas can induce cell death through the extrinsic pathway of apoptosis in a variety of cells, including developing thymocytes. Although Fas-induced cell death has been researched and modeled extensively, most of the studies have been done in vitro because of the lethality of Fas triggering in vivo. Thus, little is known about the time line of this type of cell death in vivo, specifically, how does the presence of macrophages and pro-survival cytokines affect apoptosis progression. In addition, although the sequence and timing of events during intrinsic pathway activation in thymocytes in situ have been described, no corresponding data for the extrinsic pathway are available. To address this gap in our knowledge, we established a novel system to study Fas-induced thymocyte cell death using tissue explants. We found that within 1 h of Fas ligation, caspase 3 was activated, within 2 h phosphatidylserine was externalized to serve as an “eat-me” signal, and at the same time, we observed signs of cell loss, likely due to efferocytosis. Both caspase 3 activation and phosphatidylserine exposure were critical for cell loss. Although Fas ligand (FasL) was delivered simultaneously to all cells, we observed significant variation in the entry into the cell death pathway. This model also allowed us to revisit the role of Fas in negative selection, and we ruled out an essential part for it in the deletion of autoreactive thymocytes. Our work provides a timeline for the apoptosis-associated events following Fas triggering in situ and confirms the lack of involvement of Fas in the negative selection of thymocytes.
    Keywords Fas ; thymocytes ; apoptosis ; negative selection ; FasL ; caspase 3 ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2020-10-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    Inter-library loan at ZB MED

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  3. Article ; Online: A role for phagocytosis in inducing cell death during thymocyte negative selection

    Nadia S Kurd / Lydia K Lutes / Jaewon Yoon / Shiao Wei Chan / Ivan L Dzhagalov / Ashley R Hoover / Ellen A Robey

    eLife, Vol

    2019  Volume 8

    Abstract: Autoreactive thymocytes are eliminated during negative selection in the thymus, a process important for establishing self-tolerance. Thymic phagocytes serve to remove dead thymocytes, but whether they play additional roles during negative selection ... ...

    Abstract Autoreactive thymocytes are eliminated during negative selection in the thymus, a process important for establishing self-tolerance. Thymic phagocytes serve to remove dead thymocytes, but whether they play additional roles during negative selection remains unclear. Here, using a murine thymic slice model in which thymocytes undergo negative selection in situ, we demonstrate that phagocytosis promotes negative selection, and provide evidence for the escape of autoreactive CD8 T cells to the periphery when phagocytosis in the thymus is impaired. We also show that negative selection is more efficient when the phagocyte also presents the negative selecting peptide. Our findings support a model for negative selection in which the death process initiated following strong TCR signaling is facilitated by phagocytosis. Thus, the phagocytic capability of cells that present self-peptides is a key determinant of thymocyte fate.
    Keywords central tolerance ; negative selection ; thymocyte ; phagocytosis ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Subject code 519
    Language English
    Publishing date 2019-12-01T00:00:00Z
    Publisher eLife Sciences Publications Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

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  4. Article ; Online: Equilibrative Nucleoside Transporter 3 Regulates T Cell Homeostasis by Coordinating Lysosomal Function with Nucleoside Availability

    Chin-Wen Wei / Chia-Ying Lee / Ding-Jin Lee / Chang-Feng Chu / Ju-Chu Wang / Tien-Chiao Wang / Wann-Neng Jane / Zee-Fen Chang / Chuen-Miin Leu / Ivan L. Dzhagalov / Chia-Lin Hsu

    Cell Reports, Vol 23, Iss 8, Pp 2330-

    2018  Volume 2341

    Abstract: Summary: T cells are a versatile immune cell population responding to challenges by differentiation and proliferation followed by contraction and memory formation. Dynamic metabolic reprogramming is essential for T cells to meet the biosynthetic needs ... ...

    Abstract Summary: T cells are a versatile immune cell population responding to challenges by differentiation and proliferation followed by contraction and memory formation. Dynamic metabolic reprogramming is essential for T cells to meet the biosynthetic needs and the reutilization of biomolecules, processes that require active participation of metabolite transporters. Here, we show that equilibrative nucleoside transporter 3 (ENT3) is highly expressed in peripheral T cells and has a key role in maintaining T cell homeostasis by supporting the proliferation and survival of T cells. ENT3 deficiency leads to an enlarged and disturbed lysosomal compartment, resulting in accumulation of surplus mitochondria, elevation of intracellular reactive oxygen species, and DNA damage in T cells. Our results identify ENT3 as a vital metabolite transporter that supports T cell homeostasis and activation by regulating lysosomal integrity and the availability of nucleosides. Moreover, we uncovered that T cell lysosomes are an important source of salvaged metabolites for survival and proliferation. : A sufficient supply of biomaterials is essential during T cell differentiation and proliferation. Wei et al. reveal that the nucleoside transporter ENT3 is necessary for maintaining T cell homeostasis and survival by regulating lysosome function and nucleoside availability. Keywords: T cell, metabolism, nucleoside, nucleoside transporter, ENT3, Slc29a3, lysosome
    Keywords Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2018-05-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

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