Modulation of Immune Responses by Exosomes Derived from Antigen-Presenting Cells

Shenoda, Botros; Ajit, Seena K.

doi:10.4137/cpath.s39925

Cited by 75 publications

(68 citation statements)

References 89 publications

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“…A previous study showed that HSP70 plays a critical role in liver IR injury [15]. During kidney ischemia, CD11c+ dendritic cells and/or F4/80+ macrophages are the main source of HSP70 expression [29].…”

Section: Resultsmentioning

confidence: 99%

“…Reportedly, exosomes derived from antigen-presenting cells activate T and B cells and have been explored for their immune-stimulatory properties in cancer therapy. The immunosuppressive properties of exosomes derived from macrophages and DCs reduced inflammation in animal models of several inflammatory disorders [15, 34]. In autochthonous hepatocellular carcinoma mouse models, DEXs treated in the tumor microenvironment reduced the number of Tregs and the serum concentrations of IL-10 and TGF-β [35].…”

Section: Discussionmentioning

confidence: 99%

“…Exosomes are small double-membrane vesicles secreted via exocytosis from DCs, macrophages, T cells and cells of other tissue origins under physiological and pathological conditions. Furthermore, the exosomes from antigen-presenting cells can confer therapeutic benefits by attenuating or stimulating the immune response [15]. A recent study showed that dendritic cell-derived exosomes (DEXs) deliver antigen-specific signals and can be regarded as inert vehicles that mimic DCs and activate T cells [16].…”

Section: Introductionmentioning

confidence: 99%

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Exosomes Derived from Dendritic Cells Attenuate Liver Injury by Modulating the Balance of Treg and Th17 Cells After Ischemia Reperfusion

Zheng¹,

Li²,

Wei³

et al. 2018

Cell Physiol Biochem

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Background/Aims: The present study aimed to evaluate the effects as well as the underlying mechanisms of bone marrow-derived dendritic cells (BMDCs) and exosomes produced by BMDCs (DEXs) on hepatic ischemia-reperfusion (I/R) injury (IRI). Methods: Primary hepatocytes were isolated and used to mimic the liver IR microenvironment. BMDCs were induced and characterized both biochemically with a flow cytometer (FCM) and biophysically with a microscope. Then, we exposed BMDCs to the supernatants from primary hepatocytes and evaluated the maturation of BMDCs by FCM. BMDCs were systemically injected into mice before liver IR via the tail vein, and the therapeutic effects were evaluated. The serum levels of transaminases (aspartate aminotransferase (AST) and alanine aminotransferase (ALT), inflammatory cytokines, and histological changes were respectively examined by ELISA, RT-qPCR and microscopy. Furthermore, we isolated DEXs by ultracentrifugation, characterized DEXs by transmission electron microscopy (TEM) and nanosight tracking analysis (NTA) and western blotting (WB), and then we co-cultured BMDCs/DEXs and naïve T cells and performed FCM, ELISA and confocal imaging. Moreover, we injected DEXs into mice prior to liver IR via the tail vein and examined its therapeutic effects by microscopy and ELISA. Finally, inhibitors of HSP70 (cmHSP70.1), PI3K (BKM120) and mTOR (Rapamycin) were used to investigate the role of HSP70 and the PI3K/mTOR axis in the effects of DEXs on naïve T cells by WB and FCM. Results: Bone marrow cells were efficiently induced into dendritic cells (DCs) with typical DC characteristics. The supernatants from primary hepatocytes exposed to H/R upregulated DC maturation markers. After DC administration, liver IR injury was improved with histopathological scores and serum transaminases. Additionally, we found that the anti-inflammatory cytokines TGF-β, Foxp3 and interleukin (IL)-10 were upregulated and that IL-17 was downregulated. Furthermore, confocal imaging revealed that the uptake of H/R-DEXs by naïve T cells was greater than that of DEXs derived from the control or negative group of BMDCs, and this increase was correlated with a significantly greater degree of differentiation of Tregs and Th17 cells. Moreover, H/R-DEXs administration improved liver function in mice after IR. Finally, the inhibition of HSP70, PI3K and mTOR completely abolished the effect of DEXs on naïve T cells. Conclusion: These results demonstrated that BMDCs and DEXs could alleviate hepatic I/R injury via modulating the balance between Tregs and Th17 cells. DEXs transported HSP70 into naïve T cells and stimulated the PI3K/mTOR axis to modulate the balance between Tregs and Th17 cells and protect the liver from IR injury.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Exosomes Derived from Dendritic Cells Attenuate Liver Injury by Modulating the Balance of Treg and Th17 Cells After Ischemia Reperfusion

Zheng¹,

Li²,

Wei³

et al. 2018

Cell Physiol Biochem

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“…DC-derived exosomes also serve as a communication tool with other immune cells such as T cells and B cells (47).…”

Section: The Immunization With Dcs Also Resulted In Enhanced Productimentioning

confidence: 99%

An immunoregulatory role of dendritic cell-derived exosomes versus HIV-1 infection: take it easy but be warned

Chistiakov¹,

Grechko²,

Orekhov³

et al. 2017

Ann. Transl. Med.

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“…Exosomes generated by immune cells have been studied extensively. For instance, exosomes from antigen-presenting cells including dendritic cells (DCs), B cells, and macrophages carry surface MHCI and MHCII molecules and thus directly stimulate CD8 + and CD4 + T cell responses, respectively [15,35]. Besides, Okoye et al demonstrated that Let-7d-containing exosomes derived from primary regulatory T cells (Tregs) inhibited Th1 cell responses by targeting Cox-2 in a mouse model of colitis [36].…”

Section: Introductionmentioning

confidence: 99%

Recent advances of exosomes in immune-mediated eye diseases

Zhao

Wei

et al. 2019

Stem Cell Res Ther

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Exosomes, nanosized extracellular vesicles of 30–150 nm, are shed by almost all cell types. Bearing proteins, lipids, RNAs, and DNAs, exosomes have emerged as vital biological mediators in cell-to-cell communication, affecting a plethora of physiological and pathological processes. Particularly, mounting evidence indicates that immunologically active exosomes can regulate both innate and adaptive immune responses. Herein, we review recent advances in the research of exosomes in several immune-mediated eye diseases, including Sjögren’s syndrome (SS) dry eye, corneal allograft rejection, autoimmune uveitis, and age-related macular degeneration (AMD). Additionally, we discuss the potential of exosomes as novel biomarkers and drug delivery vesicles for the diagnosis and treatment of eye diseases.

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Modulation of Immune Responses by Exosomes Derived from Antigen-Presenting Cells

Cited by 75 publications

References 89 publications

Exosomes Derived from Dendritic Cells Attenuate Liver Injury by Modulating the Balance of Treg and Th17 Cells After Ischemia Reperfusion

Exosomes Derived from Dendritic Cells Attenuate Liver Injury by Modulating the Balance of Treg and Th17 Cells After Ischemia Reperfusion

An immunoregulatory role of dendritic cell-derived exosomes versus HIV-1 infection: take it easy but be warned

Recent advances of exosomes in immune-mediated eye diseases

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