Exosomal regulation of lymphocyte homing to the gut

Park, Eun Jeong; Prajuabjinda, Onmanee; Soe, Zay Yar; Darkwah, Samuel; Appiah, Michael G; Kawamoto, Eiji; Momose, Fumiyasu; Shiku, Hiroshi; Shimaoka, Motomu

doi:10.1182/bloodadvances.2018024877

Cited by 56 publications

(61 citation statements)

References 53 publications

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“…Due to their prominent stability, long circulating half‐life and favorable safety profile, exosomes emerge as promising drug delivery vehicles that are able to deliver cargoes into the cytoplasm with minimal toxicity . Furthermore, exosomes possess a unique “homing” effect, i.e., the ability to target the cell type from which exosomes are produced . Therefore, exosomes are poised to become a rising star as effective drug delivery vehicles.…”

Section: Introductionmentioning

confidence: 99%

Exosomes and Nanoengineering: A Match Made for Precision Therapeutics

et al. 2019

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Intense efforts from both scientists and physicians across Australia have been devoted onward advancing studies to fill the gap in understanding the biology and pathogenesis underlying cancer development. Exosomes are membrane-bound bio-nanoparticles secreted or released by most cells into the extracellular space. There has been an increasing interest in such bio-nanoparticles over the past 10 years, evident from the publication number of only 324 papers in 2006 to a massive increase to 4603 publications in 2018 with the search term "exosome" based on title/abstract in PubMed. Among these studies, 151 articles published from 2007 to 2018 are from Australian institutions, with 33 papers published in 2018. Such a strong surge of interest is due to discoveries that exosomes play key roles in intercellular and intertissue communication mediated by virtue of cargos contained inside the membrane-confined space. Furthermore, exosome cargos, including proteins, mRNAs and miRNAs, are linked to the Targeted exosomal delivery systems for precision nanomedicine attract wide interest across areas of molecular cell biology, pharmaceutical sciences, and nanoengineering. Exosomes are naturally derived 50-150 nm nanovesicles that play important roles in cell-to-cell and/or cell-to-tissue communications and cross-species communication. Exosomes are also a promising class of novel drug delivery vehicles owing to their ability to shield their payload from chemical and enzymatic degradations as well as to evade recognition by and subsequent removal by the immune system. Combined with a new class of affinity ligands known as aptamers or chemical antibodies, molecularly targeted exosomes are poised to become the next generation of smartly engineered nanovesicles for precision medicine. Here, recent advances in targeted exosomal delivery systems engineered by aptamer for future strategies to promote human health using this class of human-derived nanovesicles are summarized.The ORCID identification number(s) for the author(s) of this article can be found under https://doi.

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Section: Introductionmentioning

confidence: 99%

Exosomes and Nanoengineering: A Match Made for Precision Therapeutics

et al. 2019

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“…The signaling cascade elicited by inflammatory mediators upregulates MAdCAM-1 expression; for example, in the gut tissues of inflammatory bowel diseases, MAdCAM-1 expression is augmented, thereby promoting the accumulation of aberrantly activated Tlymphocytes expressing integrin α4β7. The recent work by Park et al [4] revealed a new regulatory mechanism driven by exosomes secreted from the gut-tropic T lymphocytes that suppresses MAdCAM-1 expression in HEVs (Fig. 1a).…”

Section: Immune Lymphocyte Traffickingmentioning

confidence: 92%

“…Simultaneous to acquiring the ability to better home to the gut, gut tropic lymphocytes secrete exosomes that carry high levels of integrin α4β7 on the surface. Exosomal α4β7 integrins are functionally active and remain competent for binding to MAdCAM-1 [4]. When injected into mice, α4β7 integrin-expressing T-cell exosomes are preferentially distributed to the gut mucosa in an integrindependent manner, as is observed with gut-tropic T lymphocytes [4].…”

Section: Exosomoal Regulation Of Lymphocyte Homingmentioning

confidence: 98%

“…Exosomal α4β7 integrins are functionally active and remain competent for binding to MAdCAM-1 [4]. When injected into mice, α4β7 integrin-expressing T-cell exosomes are preferentially distributed to the gut mucosa in an integrindependent manner, as is observed with gut-tropic T lymphocytes [4]. Remarkably, α4β7 integrin-expressing T-cell exosomes are enriched with a set of microRNAs that target NKX2.3, thereby suppressing MAdCAM-1 expression [4].…”

Section: Exosomoal Regulation Of Lymphocyte Homingmentioning

confidence: 99%

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Targeted remodeling of breast cancer and immune cell homing niches by exosomal integrins

et al. 2020

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Exosomes represent an important subset of extracellular vesicles involved in inter-cellular communications in health and diseases. Exosomes secreted from cancer and immune cells travel to the specific tissues containing homing niches. The exosomes reaching the niches dynamically modify the gene expression and molecular architectures of the homing niche micro-environments. Cell adhesion molecule integrins regulate the tissue-specific homing patterns of not only cancer and immune cells, but also of the exosomes secreted from those cells. The exosomemediated remodeling of the homing niches would affect immune lymphocyte migration and host defense, as well as cancer metastasis, thereby representing a potential therapeutic target.

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“…(17,22,102) Which types of recipient cells are using these mechanisms is not well delineated. If receptor-mediated endocytosis renders the specificity of the interaction between exosome and recipient cell, cell adhesion molecules will be involved (103)(104)(105)(106)(107)(108)(109)(110). Among four groups of cell adhesion molecules (CAMs) of immunoglobulin (Ig) superfamily, cadherin, integrin and C-type lectin-domain proteins (CTLD), integrins received attention as the first paper of organotropism reported that the formation of premetastatic niche was made possible by delivery of exosomes having α6β4 (for laminin) and α6β1 to the lungs and αvβ5 (for vitronectin) for the liver (111) ( Figure 8A).…”

Section: Specificity Of Exosomes Uptake and Therapeutic Effectsmentioning

confidence: 99%

Physiologic constraints of using exosomes in vivo as systemic delivery vehicles

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Kang

et al. 2019

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Systemic delivery of exosomes meets hurdles which had not been elucidated using live molecular imaging for their biodistribution. Production and uptake of endogenous exosomes are expected to be nonspecific and specific, respectively, where external stimuli of production of exosomes and their quantitative degree of productions are not understood. Despite this lack of understanding of basic physiology of in vivo behavior of exosomes including their possible paracrine or endocrine actions, many engineering efforts are taken to develop therapeutic vehicles. Especially, the fraction of exosomes’ taking the routes of waste disposal and exerting target actions are not characterized after systemic administration. Here, we reviewed the literature about in vivo distribution and disposal/excretion of exogenous or endogenous exosomes and, from these limited resources of knowledge currently available, summarized the knowledge and the uncertainties of exosomes on physiologic standpoints. An eloquent example of the investigations to understand the roles and confounders of exosomes’ action in the brain was highlighted with emphasis on the recent discovery of brain lymphatics and hypothesis of glymphatic/lymphatic clearance pathways in diseases as well as in physiologic processes. The possibility of delivering therapeutic exosomes through the systemic circulation, across blood-brain barriers and finally to target cells such as microglia, astrocytes and/or neurons is a good testbed in which the investigators can formulate problems to solve for both understanding (science) and application (engineering).

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Exosomal regulation of lymphocyte homing to the gut

Cited by 56 publications

References 53 publications

Exosomes and Nanoengineering: A Match Made for Precision Therapeutics

Exosomes and Nanoengineering: A Match Made for Precision Therapeutics

Targeted remodeling of breast cancer and immune cell homing niches by exosomal integrins

Physiologic constraints of using exosomes in vivo as systemic delivery vehicles

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