Dendritic-cell trafficking to lymph nodes through lymphatic vessels

Randolph, Gwendalyn J.; Angeli, Véronique; Swartz, Melody A.

doi:10.1038/nri1670

Cited by 986 publications

(883 citation statements)

References 116 publications

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“…However, we show that interstitial spaces near the skin‐draining lymphatics had less macrophage accumulation in the apoA‐I‐injected mice compared with the diet switch‐ or the BSA‐injected control group. Following contact sensitization on the back‐skin dermis,40 we also show that dendritic cells are more potent to migrate to the corresponding draining lymph nodes when lipid‐free apoA‐I is injected, compared with the 2 control groups. Our results suggest that apoA‐I, but not diet switch, can regulate immune cell content and improve lymphatic function before influencing obesity‐related parameters such as subcutaneous fat accumulation.…”

Section: Discussionmentioning

confidence: 64%

“…To test whether apoA‐I might exert its beneficial effects through its interaction with the lymphatic system, we first measured the transport of dendritic cells from the peripheral tissue (skin) to the corresponding draining LN through the lymphatic system in our different groups 40. We show that apoA‐I treatment rescues lymphatic function in atherosclerotic HFD‐fed Ldlr −/− mice, with respect to the number of dendritic cells that have migrated from the skin to the corresponding draining LN (Figure 2A).…”

Section: Resultsmentioning

confidence: 99%

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Apolipoprotein A‐I Modulates Atherosclerosis Through Lymphatic Vessel‐Dependent Mechanisms in Mice

Milasan

Jean

Dallaire

et al. 2017

JAHA

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BackgroundSubcutaneously injected lipid‐free apoA‐I (apolipoprotein A‐I) reduces accumulation of lipid and immune cells within the aortic root of hypercholesterolemic mice without increasing high‐density lipoprotein–cholesterol concentrations. Lymphatic vessels are now recognized as prerequisite players in the modulation of cholesterol removal from the artery wall in experimental conditions of plaque regression, and particular attention has been brought to the role of the collecting lymphatic vessels in early atherosclerosis‐related lymphatic dysfunction. In the present study, we address whether and how preservation of collecting lymphatic function contributes to the protective effect of apoA‐I.Methods and ResultsAtherosclerotic Ldlr −/− mice treated with low‐dose lipid‐free apoA‐I showed enhanced lymphatic transport and abrogated collecting lymphatic vessel permeability in atherosclerotic Ldlr −/− mice when compared with albumin‐control mice. Treatment of human lymphatic endothelial cells with apoA‐I increased the adhesion of human platelets on lymphatic endothelial cells, in a bridge‐like manner, a mechanism that could strengthen endothelial cell–cell junctions and limit atherosclerosis‐associated collecting lymphatic vessel dysfunction. Experiments performed with blood platelets isolated from apoA‐I‐treated Ldlr −/− mice revealed that apoA‐I decreased ex vivo platelet aggregation. This suggests that in vivo apoA‐I treatment limits platelet thrombotic potential in blood while maintaining the platelet activity needed to sustain adequate lymphatic function.ConclusionsAltogether, we bring forward a new pleiotropic role for apoA‐I in lymphatic function and unveil new potential therapeutic targets for the prevention and treatment of atherosclerosis.

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Section: Discussionmentioning

confidence: 64%

Section: Resultsmentioning

confidence: 99%

Apolipoprotein A‐I Modulates Atherosclerosis Through Lymphatic Vessel‐Dependent Mechanisms in Mice

Milasan

Jean

Dallaire

et al. 2017

JAHA

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“…Lymphatic vessels bring peripheral antigens and antigen presenting cells (APCs) like dendritic cells (DCs) to lymph nodes (LNs) where adaptive immunity can be initiated. This occurs either from lymph-borne antigen capture by B cells and lymph node resident APCs [2][3][4], or by the more classical route of peripherally-activated DC migration to the LN and activation of resident T cells [5]. Lymph nodes are also important centers for the maintenance of tolerance to self-antigens [4,[6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Role of Lymphatic Vessels in Tumor Immunity: Passive Conduits or Active Participants?

Lund

Swartz

2010

J Mammary Gland Biol Neoplasia

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Research in lymphatic biology and cancer immunology may soon intersect as emerging evidence implicates the lymphatics in the progression of chronic inflammation and autoimmunity as well as in tumor metastasis and immune escape. Like the blood vasculature, the lymphatic system comprises a highly dynamic conduit system that regulates fluid homeostasis, antigen transport and immune cell trafficking, which all play important roles in the progression and resolution of inflammation, autoimmune diseases, and cancer. This review presents emerging evidence that lymphatic vessels are active modulators of immunity, perhaps fine-tuning the response to adjust the balance between peripheral tolerance and immunity. This suggests that the tumor-associated lymphatic vessels and draining lymph node may be important in tumor immunity which in turn governs metastasis.

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“…Antigen-bearing DCs then migrate to draining lymph nodes (LNs) and efficiently stimulate antigen-specific T cells via MHC molecules. 2 Despite the widespread use of DCs in tumor vaccination protocols, 3 the limited clinical success of DC vaccines necessitates new methodologies for improving DC vaccine potency. 4 Several methods for manipulating antigen-presenting DCs have been developed in experimental studies and applied in clinical trials.…”

Section: Introductionmentioning

confidence: 99%

Engineering of highly immunogenic long-lived DC vaccines by antiapoptotic protein gene transfer to enhance cancer vaccine potency

et al. 2008

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Dendritic cells (DCs) have a critical role in the induction of antigen-specific immune responses, transporting antigens from peripheral tissue to regional lymph nodes where they interact with antigen-specific T lymphocytes. Recent studies revealed that the efficacy of the T cell-dependent immune response depends on the lifespan of the antigen-presenting DCs in the lymph nodes. Here, we succeeded in engineering long-lived antigen-presenting DCs via Bcl-x L -derived hyperactive mutant antiapoptotic protein (Bcl-x FNK ) gene transfer. In a B16BL6 melanoma model, these long-lived DCs exerted potent antitumor immunity that depended mainly on antigenspecific cytotoxic T lymphocytes. Furthermore, in vivo longevity of the long-lived DC vaccine led to antigen-specific activation of interferon-g-producing CD4 + and CD8 + T cells. Thus, the long-lived DC vaccine strategy is highly useful for constructing DC vaccines, as well as other cell-based medicines, such as stem cell therapy.

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Dendritic-cell trafficking to lymph nodes through lymphatic vessels

Cited by 986 publications

References 116 publications

Apolipoprotein A‐I Modulates Atherosclerosis Through Lymphatic Vessel‐Dependent Mechanisms in Mice

Apolipoprotein A‐I Modulates Atherosclerosis Through Lymphatic Vessel‐Dependent Mechanisms in Mice

Role of Lymphatic Vessels in Tumor Immunity: Passive Conduits or Active Participants?

Engineering of highly immunogenic long-lived DC vaccines by antiapoptotic protein gene transfer to enhance cancer vaccine potency

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