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  • The American Association of Immunologists  (3)
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  • The American Association of Immunologists  (3)
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  • 1
    Online Resource
    Online Resource
    The American Association of Immunologists ; 2008
    In:  The Journal of Immunology Vol. 181, No. 8 ( 2008-10-15), p. 5242-5248
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 181, No. 8 ( 2008-10-15), p. 5242-5248
    Abstract: Exosomes released from different types of cells have been proposed to contribute to intercellular communication. We report that thymic exosome-like particles (ELPs) released from cells of the thymus can induce the development of Foxp3+ regulatory T (Treg) cells in the lung and liver. Thymic ELPs also induce the conversion of thymic CD4+CD25− T cells into Tregs. Tregs induced by thymic ELPs suppress the proliferation of CD4+CD25− T cells in vitro and in vivo. We further show that neutralization of TGF-β in ELPs partially reverses thymic ELP-mediated induction of CD4+Foxp3+ T cells in the lung and liver. This study demonstrates that thymic ELPs participate in the induction of Foxp3+ Tregs. Also, TGF-β of thymic ELPs might be required for the generation of Tregs in the peripheral tissues.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    RVK:
    RVK:
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2008
    detail.hit.zdb_id: 1475085-5
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  • 2
    Online Resource
    Online Resource
    The American Association of Immunologists ; 2011
    In:  The Journal of Immunology Vol. 186, No. 1_Supplement ( 2011-04-01), p. 66.36-66.36
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 186, No. 1_Supplement ( 2011-04-01), p. 66.36-66.36
    Abstract: A new subset of NKT cells, an IL-17-producing iNKT cell (iNKT17), has been identified recently. The role of this new iNKT17 subset in a tumor bearing host is unknown. We report that the percentages of iNKT17 cells in the thymus are increased dramatically in naïve mice from 0.5 ± 0.1% to 2.1 ± 0.2% in 4T1 breast tumor-bearing mice. Tumor induced iNKT17 cells are marked as TCRβint CD1dTetramerpos CD4neg CD8neg CD44hi CD25hi CD5pos CD24low DX5neg CD54pos. The iNKT17 cells from 4T1 tumor bearing mice are unique in that upon α-Gelcer-CD1d tetramer stimulation, IL-17 but not IL-4, IFN-γ, IL-10, IL-13, IL-6, IL-12 is induced. The CD11b+Gr1+ myeloid-derived suppressor cells (MDSC) accumulate in dramatic fashion in the thymus in 4T1 tumor bearing mice. The induction of iNKT17 subset is MDSC dependent. Addition of antibodies against TGFβ or IL-6 leads to the inhibition of MDSC-mediated induction of iNKT17 cells, suggesting that TGFβ and IL-6 are required for the induction. The MDSC-mediated induction of the iNKT17 cell subset is correlated with reduction of SLAM but not Ly9, CD84, Ly108 and 2B4. Mice injected intravenously with anti-IL17 antibody leads to the attenuation of 4T1 tumor metastasis to lung. This data suggest that MDSC-mediated induction of iNKT17 cells may play a role in promoting tumor metastasis.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    RVK:
    RVK:
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2011
    detail.hit.zdb_id: 1475085-5
    Location Call Number Limitation Availability
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  • 3
    Online Resource
    Online Resource
    The American Association of Immunologists ; 2010
    In:  The Journal of Immunology Vol. 184, No. 1_Supplement ( 2010-04-01), p. 95.16-95.16
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 184, No. 1_Supplement ( 2010-04-01), p. 95.16-95.16
    Abstract: Tumor cells released membrane microvesicles - exosomes, can stimulate inflammation through MDSC, and then promote tumor growth by activating immunosuppressive networks. MyD88 is a cytoplasmic adaptor molecule essential for inducing inflammation via the TLR receptors. Very little is known about whether tumor exosome-mediated induction MDSCs and tumor growth is regulated through MyD88. In this study, we observed that mice pretreated with tumor exosomes had a significant acceleration of tumor metastasis in the lung. Tumor metastasis correlated significantly with an increase in recruitment of more MDSCs in the lung of B6 mice pretreated with tumor exosomes. These effects were blunted when MyD88 KO mice were pretreated with tumor exosomes. MDSCs induced by tumor exosomes and isolated from WT B6 mice are also more potent in inhibition of T cell activation and induction of IL-6 and TNF-α than MDSCs isolated from the lung of MyD88 KO mice via activation of the Stat3 pathway. Our in vitro data further support that addition of tumor exosomes to bone marrow derived CD11b+Gr-1+ cells isolated from WT B6 mice results in producing more cytokines, including TNF-α, IL-6 and the chemokine CCL2, than CD11b+Gr-1+ cells isolated from MyD88 KO mice. Less CCL2 in lung was observed in MyD88 KO mice pretreated with tumor exosomes than that in WT mice. Together these data demonstrate a pivotal role for MyD88 in tumor exosome-mediated induction of IL-6, TNF-α, expansion of MDSCs and tumor metastasis.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    RVK:
    RVK:
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2010
    detail.hit.zdb_id: 1475085-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
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