Regulation of chronic inflammatory and immune processes by extracellular vesicles

Robbins, Paul D.; Dorronsoro, Akaitz; Booker, Cori N.

doi:10.1172/jci81131

Cited by 232 publications

(206 citation statements)

References 102 publications

(109 reference statements)

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“…EVs are comprised of both microvesicles, released from the plasma membrane by shedding, and nanovesicles or exosomes, generated by reverse budding of multivesicular bodies (MVBs) (47,48). These different types of EVs are characterized predominantly by their size, with exosomes ranging from 30 to 100 nm and microvesicles usually being larger than 100 nm.…”

Section: Evsmentioning

confidence: 99%

“…Although their contents likely differ, both small and large EVs are enriched for a subset of diverse proteins, lipids, messenger RNAs (mRNAs), and non-coding RNAs (ncRNAs), such as miRNAs, which are derived from the parental cells. EVs have a variety of reported functions and some of their betterdocumented activities are associated with some form of immune regulation (47,48). EVs from both immune and non-immune cells, such as MSCs and endothelial cells, contribute to antigen-specific and non-specific immune regulation (47)(48)(49).…”

Section: Evsmentioning

confidence: 99%

“…EVs have a variety of reported functions and some of their betterdocumented activities are associated with some form of immune regulation (47,48). EVs from both immune and non-immune cells, such as MSCs and endothelial cells, contribute to antigen-specific and non-specific immune regulation (47)(48)(49). Depending upon the context and vesicle type, EVs can stimulate or suppress the immune responses to infections with viruses and microbial pathogens as well as cancer.…”

Section: Evsmentioning

confidence: 99%

“…For examples, tumor associated proteins such as EGF-R (glioblastoma) (61) or oncogene mRNAs (62) have been found in cerebral spinal fluid or blood-derived EVs respectively whereas the protein glypican-1 is found in circulating EVs from patients with pancreatic cancer (63). Also, circulating EVs have important biological activities (47,48). Serum-derived EVs from mice bearing tumors were able to suppress tumor antigen-specific responses (64)(65)(66).…”

Section: Circulating Blood-borne Vesiclesmentioning

confidence: 99%

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Extracellular vesicles and aging

Robbins¹

2017

Stem Cell Investig.

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AgingIt is estimated that in the next 20 years, the number of individuals in the United States over the age of 65 will double, numbering more than 70 million individuals. Unfortunately, as we age there is an unavoidable and progressive loss of the ability to maintain tissue homeostasis under stress and an attrition of functional reserve. As a consequence, the incidence of numerous debilitating diseases increases nearly exponentially with age, including cardiovascular disease, neurodegeneration, diabetes, osteoarthritis, and osteoporosis. Over 90% of individuals >65 years of age have at least one chronic disease, while >70% have at least two. These chronic diseases account for 75% of our healthcare costs, amounting to approximately $3 trillion in costs last year alone. Indeed, chronic diseases of the elderly are the greatest healthcare burden in the United States and seriously impact the quality of life of a large segment of the population. Thus, there is a significant need to understand mechanisms driving aging and to develop novel therapeutics. Given the diverse roles of blood-borne EVs in modulating not only the immune response, but also angiogenesis and tissue regeneration, they likely play a key role in modulating the aging process. This review focuses on the role EVs could play in aging, their therapeutic application for extending healthspan and their potential for use as biomarkers of unhealthy aging. Abstract: Aging and the chronic diseases associated with aging place a tremendous burden on our healthcare system. As our world population ages dramatically over the next decades, this will only increase.Hence, there is a great need to discover fundamental mechanisms of aging to enable development of strategies for minimizing the impact of aging on our health and economy. There is general agreement that cell autonomous mechanisms contribute to aging. As cells accrue damage over time, they respond to it by triggering individual cell fate decisions that ultimately disrupt tissue homeostasis and thus increase risk of morbidity. However, there are numerous lines of evidence, including heterochronic parabiosis and plasma transfer, indicating that cell non-autonomous mechanisms are critically important for aging as well. In addition, senescent cells, which accumulate in tissues with age, can display a senescence-associated secretory phenotype (SASP) that contributes to driving aging and loss of tissue homeostasis through a non-cell autonomous mechanism(s). Given the diverse roles of blood-borne extracellular vesicles (EVs) in modulating not only the immune response, but also angiogenesis and tissue regeneration, they likely play a key role in modulating the aging process through cell non-autonomous mechanisms. The fact that senescent cells release more EVs and with a different composition suggests they contribute to the adverse effects of senescence on aging. In addition, the ability of EVs from functional progenitor cells to promote tissue regeneration suggests that stem cell-derived EVs could be used therapeutica...

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Section: Evsmentioning

confidence: 99%

Section: Evsmentioning

confidence: 99%

Section: Evsmentioning

confidence: 99%

Section: Circulating Blood-borne Vesiclesmentioning

confidence: 99%

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Extracellular vesicles and aging

Robbins¹

2017

Stem Cell Investig.

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“…Blockage of the CXCL1 receptor CXCR1/2 ameliorated alcoholic steatohepatitis in mice (14). In addition to chemokines, extracellular vesicles (EVs) are new players in cellto-cell communication and play an important role in promoting inflammation and neutrophil infiltration in a variety of diseases (15,16), including liver diseases (17)(18)(19)(20)(21)(22)(23)(24)(25). EVs are nanometer-sized, membrane-bound extracellular milieu vesicles derived from cells (17).…”

Section: Introductionmentioning

confidence: 99%