17 research outputs found

    Regulation of Immune Function by the Lymphatic System in Lymphedema

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    The lymphatic vasculature has traditionally been thought to play a passive role in the regulation of immune responses by transporting antigen presenting cells and soluble antigens to regional lymph nodes. However, more recent studies have shown that lymphatic endothelial cells regulate immune responses more directly by modulating entry of immune cells into lymphatic capillaries, presenting antigens on major histocompatibility complex proteins, and modulating antigen presenting cells. Secondary lymphedema is a disease that develops when the lymphatic system is injured during surgical treatment of cancers or is damaged by infections. We have used mouse models of lymphedema in order to understand the effects of chronic lymphatic injury on immune responses and have shown that lymphedema results in a mixed T helper cell and T regulatory cell (Treg) inflammatory response. Prolonged T helper 2 biased immune responses in lymphedema regulate the pathology of this disease by promoting tissue fibrosis, inhibiting formation of collateral lymphatics, decreasing lymphatic vessel pumping capacity, and increasing lymphatic leakiness. Treg infiltration following lymphatic injury results from proliferation of natural Tregs and suppresses innate and adaptive immune responses. These studies have broad clinical relevance since understanding how lymphatic injury in lymphedema can modulate immune responses may provide a template with which we can study more subtle forms of lymphatic injury that may occur in physiologic conditions such as aging, obesity, metabolic tumors, and in the tumor microenvironment

    Visualization 1: Calculation of reflectance distribution using angular spectrum convolution in mesh-based computer generated hologram

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    movie clip for uniform mesh phase simulation Originally published in Optics Express on 22 August 2016 (oe-24-17-19801

    Visualization 2: Calculation of reflectance distribution using angular spectrum convolution in mesh-based computer generated hologram

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    movie clip for diffuse mesh surface simulation Originally published in Optics Express on 22 August 2016 (oe-24-17-19801

    Turn-on Fluorescent Chemosensor Based on an Amino Acid for Pb(II) and Hg(II) Ions in Aqueous Solutions and Role of Tryptophan for Sensing

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    This communication presents a fluorescent chemosensor for detecting Pb(II) and Hg(II) in aqueous solutions. The sensor showed a turn-on response to Pb(II) by an enhancement of emission intensity at 380 nm and to Hg(II) by an enhancement of emission intensities at 380 and 475 nm. We have first characterized a unique function of tryptophan as a ligand as well as a quencher for recognition and fluorescent change by a metal binding event

    Highly Enantioselective Total Synthesis of (+)-Isonitramine

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    A new efficient enantioselective synthetic method of (+)-isonitramine is reported. (+)-Isonitramine was obtained in 12 steps (98% ee and 43% overall yield) from δ-valerolactam <i>via</i> enantioselective phase-transfer catalytic alkylation, Dieckman condensation, and diastereoselective reduction as key steps

    Tumor-Associated Lymphatics Upregulate MHC-II to Suppress Tumor-Infiltrating Lymphocytes

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    Steady-state lymphatic endothelial cells (LECs) can induce peripheral tolerance by presenting endogenous antigens on MHC class I (MHC-I) molecules. Recent evidence suggests that lymph node LECs can cross-present tumor antigens on MHC-I to suppress tumor-specific CD8+ T cells. Whether LECs can act as immunosuppressive cells in an MHC-II dependent manner in the local tumor microenvironment (TME) is not well characterized. Using murine heterotopic and spontaneous tumor models, we show that LECs in the TME increase MHC-II expression in the context of increased co-inhibitory signals. We provide evidence that tumor lymphatics in human melanoma and breast cancer also upregulate MHC-II compared to normal tissue lymphatics. In transgenic mice that lack LEC-specific MHC-II expression, heterotopic tumor growth is attenuated, which is associated with increased numbers of tumor-specific CD8+ and effector CD4+ T cells, as well as decreased numbers of T regulatory CD4+ cells in the TME. Mechanistically, we show that murine and human dermal LECs can take up tumor antigens in vitro. Antigen-loaded LECs in vitro can induce antigen-specific proliferation of CD8+ T cells but not CD4+ T cells; however, these proliferated CD8+ T cells have reduced effector function in the presence of antigen-loaded LECs. Taken together, our study suggests LECs can act as immunosuppressive cells in the TME in an MHC-II dependent manner. Whether this is a result of direct tumor antigen presentation on MHC-II requires additional investigation
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