Lymphatic transport of exosomes as a rapid route of information dissemination to the lymph node

Srinivasan, Savitha; Vannberg, Fredrik; Dixon, J. Brandon

doi:10.1038/srep24436

Cited by 140 publications

(151 citation statements)

References 49 publications

(63 reference statements)

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“…This property, and the fact that exosomes can carry small bits of genetic information make them potential therapeutic devices, possibly for future gene therapy approaches (913). Exosomes have been shown to preferentially enter lymphatic vessels and can be transported to lymph nodes within minutes (1016). The functional role may be to prime cells in the lymph node ahead of the arrival of antigen present cells or other immune cells (1016).…”

Section: New Directions: Microparticles Nanoparticles and Immunothementioning

confidence: 99%

Lymphatic Vessel Network Structure and Physiology

Breslin

Yang

Scallan

et al. 2018

Comprehensive Physiology

264

258

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The lymphatic system is comprised of a network of vessels interrelated with lymphoid tissue, which has the holistic function to maintain the local physiologic environment for every cell in all tissues of the body. The lymphatic system maintains extracellular fluid homeostasis favorable for optimal tissue function, removing substances that arise due to metabolism or cell death, and optimizing immunity against bacteria, viruses, parasites, and other antigens. This article provides a comprehensive review of important findings over the past century along with recent advances in the understanding of the anatomy and physiology of lymphatic vessels, including tissue/organ specificity, development, mechanisms of lymph formation and transport, lymphangiogenesis, and the roles of lymphatics in disease.

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Section: New Directions: Microparticles Nanoparticles and Immunothementioning

confidence: 99%

Lymphatic Vessel Network Structure and Physiology

Breslin

Yang

Scallan

et al. 2018

Comprehensive Physiology

264

258

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show abstract

“…Control or Poly I:C exosomes (total quantity = 10 μg) were injected intradermally into the tail of eight-week-old male Balb/C mice (Charles River Laboratories, Wilmington, MA) as described previously18 and euthanized on day two (t = 48 hours). PBS was mixed with PEGylated IRdye 800CW (Licor) and injected similarly as the experimental control.…”

Section: Methodsmentioning

confidence: 99%

“…Furthermore, we recently showed that exosomes are rapidly trafficked from peripheral tissues by the lymphatics, and retained in the draining lymph node by macrophages in a murine model18.…”

mentioning

confidence: 99%

TLR-exosomes exhibit distinct kinetics and effector function

Srinivasan

Ravishankar

et al. 2017

Sci Rep

Self Cite

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The innate immune system is vital to rapidly responding to pathogens and Toll-like receptors (TLRs) are a critical component of this response. Nanovesicular exosomes play a role in immunity, but to date their exact contribution to the dissemination of the TLR response is unknown. Here we show that exosomes from TLR stimulated cells can largely recapitulate TLR activation in distal cells in vitro. We can abrogate the action-at-a-distance signaling of exosomes by UV irradiation, demonstrating that RNA is crucial for their effector function. We are the first to show that exosomes derived from poly(I:C) stimulated cells induce in vivo macrophage M1-like polarization within murine lymph nodes. These poly(I:C) exosomes demonstrate enhanced trafficking to the node and preferentially recruit neutrophils as compared to control exosomes. This work definitively establishes the differential effector function for exosomes in communicating the TLR activation state of the cell of origin.

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“…47 Cancer cells in particular secrete large quantities of TEXs, which can be found in peripherally circulating blood. 48 Consequently, blood cells are exposed to many exosomes from both normal and malignant cells, 49 which play key roles in modulating the immune system.…”

Section: Discussionmentioning

confidence: 99%

Uptake of lymphoma-derived exosomes by peripheral blood leukocytes

Bennit¹,

Gonda²,

Oppegard³

et al. 2017

BLCTT

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Exosomes are nanosized lipid vesicles secreted into blood and other body fluids and serve as vehicles for intercellular communication. Despite being an important component of the tumor microenvironment (TME), exosomal targeting and uptake into recipient cells are still not fully understood. Few studies have looked at lymphoma exosomes and their interactions with circulating blood cells. In this study, we examine the exosomal uptake distribution among peripheral blood leukocytes (PBLs) using vesicles derived from a diffuse large B cell lymphoma cell line, WSU-DLCL2. Lymphoma cells survive, proliferate, and are protected from the cytotoxic effects of chemotherapeutic agents by soluble factors or by direct contact with inflammatory and stromal cells within the TME. In an attempt to close the gap in knowledge concerning lymphoma TME immunosuppression, we have treated normal human PBLs with PKH67-labeled lymphoma exosomes and monitored the uptake by measuring fluorescence at different time points using flow cytometry and fluorescent microscopy. Our results show that of the four populations examined, B cells and monocytes demonstrated uptake of PKH67-labeled exosomes, while T cells and NK cells displayed significantly less uptake.

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Lymphatic transport of exosomes as a rapid route of information dissemination to the lymph node

Cited by 140 publications

References 49 publications

Lymphatic Vessel Network Structure and Physiology

Lymphatic Vessel Network Structure and Physiology

TLR-exosomes exhibit distinct kinetics and effector function

Uptake of lymphoma-derived exosomes by peripheral blood leukocytes

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