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  • Oxford University Press (OUP)  (3)
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  • Oxford University Press (OUP)  (3)
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  • 1
    Online Resource
    Online Resource
    Generation of Thymic Epithelial Cell Progenitors by Mouse Embryonic Stem Cells
    Oxford University Press (OUP) ; 2009
    In:  Stem Cells Vol. 27, No. 12 ( 2009-12-01), p. 3012-3020
    Details
    In: Stem Cells, Oxford University Press (OUP), Vol. 27, No. 12 ( 2009-12-01), p. 3012-3020
    Abstract: Thymopoiesisis regulated by the thymic microenvironment, of which epithelial cells are the major components. Both cortical and medullary thymic epithelial cells (TECs) have been shown to arise from a common progenitor cell. Here we show for the first time that mouse embryonic stem cells (mESCs) can be selectively induced in vitro to differentiate into cells that have the phenotype of thymic epithelial progenitors (TEPs). When placed in vivo, these mESC-derived TEPs self-renew, develop into TECs, and reconstitute the normal thymic architecture. Functionally, these ESC-derived TEPs enhanced thymocyte regeneration after bone marrow transplantation and increased the number of functional naive splenic T cells. In addition to providing a model to study the molecular events underlying thymic epithelial cell development, the ability to selectively induce the development of TEPs in vitro from mESCs has important implications regarding the prevention and/or treatment of primary and secondary T-cell immunodeficiencies. Disclosure of potential conflicts of interest is found at the end of this article.
    Type of Medium: Online Resource
    ISSN: 1066-5099 , 1549-4918
    URL: Article
    DOI: 10.1002/stem.238
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2009
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    SSG: 12
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  • 2
    Online Resource
    Online Resource
    Recombinant CD300c-Ig fusion protein attenuates collagen-induced arthritis in mice
    Oxford University Press (OUP) ; 2022
    In:  Rheumatology Vol. 61, No. 3 ( 2022-03-02), p. 1255-1264
    Details
    In: Rheumatology, Oxford University Press (OUP), Vol. 61, No. 3 ( 2022-03-02), p. 1255-1264
    Abstract: RA is a chronic autoimmune disease characterized by joint inflammation and tissue destruction. Immune responses mediated by T cells and autoantibodies are known to play critical roles in RA. Collagen type II (CII)-induced arthritis (CIA) is a commonly used animal model of human RA. We have previously reported the identification of a new T cell inhibitory molecule CD300c. Here we investigate the ability of recombinant CD300c-IgG2a Fc (CD300c-Ig) fusion protein to prevent and treat CIA. Methods Mice were induced to develop CIA by CII and injected with CD300c-Ig or control Ig protein before or after CIA symptoms occur. The mice were examined for CIA clinical and pathological scores, and analysed for the expression of proinflammatory cytokines, the percentage and activation of CD4 T cells and regulatory T cells, CII-specific T cell proliferation and cytokine production, and CII-specific autoantibody production. Results In a prevention model, CD300c-Ig significantly decreases CIA incidence, and reduces clinical and pathological arthritis scores. In the treatment model, CD300c-Ig ameliorates established CIA. The beneficial effects of CD300c-Ig are related to decreased expansion and activation of T cells in the spleen and reduced expression of proinflammatory cytokines in the joints. CD300c-Ig also inhibits CII-specific T cell proliferation and Th1 and Th17 cytokine production. In addition, CD300c-Ig treatment reduced the production of CII autoantibodies in the serum. Furthermore, CD300c-Ig inhibits the proliferation and activation of T cells from RA patients in vitro. Conclusion CD300c-Ig protein has the potential to be used in the treatment of patients with RA.
    Type of Medium: Online Resource
    ISSN: 1462-0324 , 1462-0332
    URL: Article
    DOI: 10.1093/rheumatology/keab450
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 3
    Online Resource
    Online Resource
    Transplantation of Donor-Origin Mouse Embryonic Stem Cell-Derived Thymic Epithelial Progenitors Prevents the Development of Chronic Graft-versus-Host Disease in Mice
    Oxford University Press (OUP) ; 2017
    In:  Stem Cells Translational Medicine Vol. 6, No. 1 ( 2017-01-01), p. 121-130
    Details
    In: Stem Cells Translational Medicine, Oxford University Press (OUP), Vol. 6, No. 1 ( 2017-01-01), p. 121-130
    Abstract: Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for many malignant and nonmalignant diseases. However, chronic graft-versus-host disease (cGVHD) remains a significant cause of late morbidity and mortality after allogeneic HSCT. cGVHD often manifests as autoimmune syndrome. Thymic epithelial cells (TECs) play a critical role in supporting negative selection and regulatory T-cell (Treg) generation. Studies have shown that damage in TECs is sufficient to induce cGVHD. We have previously reported that mouse embryonic stem cells (mESCs) can be selectively induced to generate thymic epithelial progenitors (TEPs) in vitro. When transplanted in vivo, mESC-TEPs further develop into TECs that support T-cell development. We show here that transplantation of donor-origin mESC-TEPs into cGVHD recipients induces immune tolerance to both donor and host antigens and prevents the development of cGVHD. This is associated with more TECs and Tregs. Our results suggest that embryonic stem cell-derived TEPs may offer a new tool to control cGVHD.
    Type of Medium: Online Resource
    ISSN: 2157-6564 , 2157-6580
    URL: Article
    DOI: 10.5966/sctm.2016-0012
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2017
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