Extracellular Vesicles Derived From Ex Vivo Expanded Regulatory T Cells Modulate In Vitro and In Vivo Inflammation
Extracellular vehicles (EVs) are efficient biomarkers of disease and participate in disease pathogenesis; however, their use as clinical therapies to modify disease outcomes remains to be determined. Cell-based immune therapies, including regulatory T cells (Tregs), are currently being clinically ev...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.875825/full |
| _version_ | 1818216858329808896 |
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| author | Aaron D. Thome Jason R. Thonhoff Weihua Zhao Alireza Faridar Jinghong Wang David R. Beers Stanley H. Appel |
| author_facet | Aaron D. Thome Jason R. Thonhoff Weihua Zhao Alireza Faridar Jinghong Wang David R. Beers Stanley H. Appel |
| author_sort | Aaron D. Thome |
| collection | DOAJ |
| description | Extracellular vehicles (EVs) are efficient biomarkers of disease and participate in disease pathogenesis; however, their use as clinical therapies to modify disease outcomes remains to be determined. Cell-based immune therapies, including regulatory T cells (Tregs), are currently being clinically evaluated for their usefulness in suppressing pro-inflammatory processes. The present study demonstrates that ex vivo expanded Tregs generate a large pool of EVs that express Treg-associated markers and suppress pro-inflammatory responses in vitro and in vivo. Intravenous injection of Treg EVs into an LPS-induced mouse model of inflammation reduced peripheral pro-inflammatory transcripts and increased anti-inflammatory transcripts in myeloid cells as well as Tregs. Intranasal administration of enriched Treg EVs in this model also reduced pro-inflammatory transcripts and the associated neuroinflammatory responses. In a mouse model of amyotrophic lateral sclerosis, intranasal administration of enriched Treg EVs slowed disease progression, increased survival, and modulated inflammation within the diseased spinal cord. These findings support the therapeutic potential of expanded Treg EVs to suppress pro-inflammatory responses in human disease. |
| first_indexed | 2024-12-12T06:58:39Z |
| format | Article |
| id | doaj.art-d4950a1a2da241859872c70b9fd4dbf0 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-12T06:58:39Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-d4950a1a2da241859872c70b9fd4dbf02022-12-22T00:33:54ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-06-011310.3389/fimmu.2022.875825875825Extracellular Vesicles Derived From Ex Vivo Expanded Regulatory T Cells Modulate In Vitro and In Vivo InflammationAaron D. ThomeJason R. ThonhoffWeihua ZhaoAlireza FaridarJinghong WangDavid R. BeersStanley H. AppelExtracellular vehicles (EVs) are efficient biomarkers of disease and participate in disease pathogenesis; however, their use as clinical therapies to modify disease outcomes remains to be determined. Cell-based immune therapies, including regulatory T cells (Tregs), are currently being clinically evaluated for their usefulness in suppressing pro-inflammatory processes. The present study demonstrates that ex vivo expanded Tregs generate a large pool of EVs that express Treg-associated markers and suppress pro-inflammatory responses in vitro and in vivo. Intravenous injection of Treg EVs into an LPS-induced mouse model of inflammation reduced peripheral pro-inflammatory transcripts and increased anti-inflammatory transcripts in myeloid cells as well as Tregs. Intranasal administration of enriched Treg EVs in this model also reduced pro-inflammatory transcripts and the associated neuroinflammatory responses. In a mouse model of amyotrophic lateral sclerosis, intranasal administration of enriched Treg EVs slowed disease progression, increased survival, and modulated inflammation within the diseased spinal cord. These findings support the therapeutic potential of expanded Treg EVs to suppress pro-inflammatory responses in human disease.https://www.frontiersin.org/articles/10.3389/fimmu.2022.875825/fullexosome (vesicle)inflammationimmune modulationneuroinflammationperipheral inflammationinflammatory disease |
| spellingShingle | Aaron D. Thome Jason R. Thonhoff Weihua Zhao Alireza Faridar Jinghong Wang David R. Beers Stanley H. Appel Extracellular Vesicles Derived From Ex Vivo Expanded Regulatory T Cells Modulate In Vitro and In Vivo Inflammation Frontiers in Immunology exosome (vesicle) inflammation immune modulation neuroinflammation peripheral inflammation inflammatory disease |
| title | Extracellular Vesicles Derived From Ex Vivo Expanded Regulatory T Cells Modulate In Vitro and In Vivo Inflammation |
| title_full | Extracellular Vesicles Derived From Ex Vivo Expanded Regulatory T Cells Modulate In Vitro and In Vivo Inflammation |
| title_fullStr | Extracellular Vesicles Derived From Ex Vivo Expanded Regulatory T Cells Modulate In Vitro and In Vivo Inflammation |
| title_full_unstemmed | Extracellular Vesicles Derived From Ex Vivo Expanded Regulatory T Cells Modulate In Vitro and In Vivo Inflammation |
| title_short | Extracellular Vesicles Derived From Ex Vivo Expanded Regulatory T Cells Modulate In Vitro and In Vivo Inflammation |
| title_sort | extracellular vesicles derived from ex vivo expanded regulatory t cells modulate in vitro and in vivo inflammation |
| topic | exosome (vesicle) inflammation immune modulation neuroinflammation peripheral inflammation inflammatory disease |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.875825/full |
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