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Transfer of extracellular vesicle‐microRNA controls germinal center reaction and antibody production
Intercellular communication orchestrates effective immune responses against disease‐causing agents. Extracellular vesicles (EVs) are potent mediators of cell–cell communication. EVs carry bioactive molecules, including microRNAs, which modulate gene expression and function in the recipient cell. Her...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7132182/ https://www.ncbi.nlm.nih.gov/pubmed/32073750 http://dx.doi.org/10.15252/embr.201948925 |
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author | Fernández‐Messina, Lola Rodríguez‐Galán, Ana de Yébenes, Virginia G Gutiérrez‐Vázquez, Cristina Tenreiro, Sandra Seabra, Miguel C Ramiro, Almudena R Sánchez‐Madrid, Francisco |
author_facet | Fernández‐Messina, Lola Rodríguez‐Galán, Ana de Yébenes, Virginia G Gutiérrez‐Vázquez, Cristina Tenreiro, Sandra Seabra, Miguel C Ramiro, Almudena R Sánchez‐Madrid, Francisco |
author_sort | Fernández‐Messina, Lola |
collection | PubMed |
description | Intercellular communication orchestrates effective immune responses against disease‐causing agents. Extracellular vesicles (EVs) are potent mediators of cell–cell communication. EVs carry bioactive molecules, including microRNAs, which modulate gene expression and function in the recipient cell. Here, we show that formation of cognate primary T‐B lymphocyte immune contacts promotes transfer of a very restricted set of T‐cell EV‐microRNAs (mmu‐miR20‐a‐5p, mmu‐miR‐25‐3p, and mmu‐miR‐155‐3p) to the B cell. Transferred EV‐microRNAs target key genes that control B‐cell function, including pro‐apoptotic BIM and the cell cycle regulator PTEN. EV‐microRNAs transferred during T‐B cognate interactions also promote survival, proliferation, and antibody class switching. Using mouse chimeras with Rab27KO EV‐deficient T cells, we demonstrate that the transfer of small EVs is required for germinal center reaction and antibody production in vivo, revealing a mechanism that controls B‐cell responses via the transfer of EV‐microRNAs of T‐cell origin. These findings also provide mechanistic insight into the Griscelli syndrome, associated with a mutation in the Rab27a gene, and might explain antibody defects observed in this pathogenesis and other immune‐related and inflammatory disorders. |
format | Online Article Text |
id | pubmed-7132182 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-71321822020-04-06 Transfer of extracellular vesicle‐microRNA controls germinal center reaction and antibody production Fernández‐Messina, Lola Rodríguez‐Galán, Ana de Yébenes, Virginia G Gutiérrez‐Vázquez, Cristina Tenreiro, Sandra Seabra, Miguel C Ramiro, Almudena R Sánchez‐Madrid, Francisco EMBO Rep Reports Intercellular communication orchestrates effective immune responses against disease‐causing agents. Extracellular vesicles (EVs) are potent mediators of cell–cell communication. EVs carry bioactive molecules, including microRNAs, which modulate gene expression and function in the recipient cell. Here, we show that formation of cognate primary T‐B lymphocyte immune contacts promotes transfer of a very restricted set of T‐cell EV‐microRNAs (mmu‐miR20‐a‐5p, mmu‐miR‐25‐3p, and mmu‐miR‐155‐3p) to the B cell. Transferred EV‐microRNAs target key genes that control B‐cell function, including pro‐apoptotic BIM and the cell cycle regulator PTEN. EV‐microRNAs transferred during T‐B cognate interactions also promote survival, proliferation, and antibody class switching. Using mouse chimeras with Rab27KO EV‐deficient T cells, we demonstrate that the transfer of small EVs is required for germinal center reaction and antibody production in vivo, revealing a mechanism that controls B‐cell responses via the transfer of EV‐microRNAs of T‐cell origin. These findings also provide mechanistic insight into the Griscelli syndrome, associated with a mutation in the Rab27a gene, and might explain antibody defects observed in this pathogenesis and other immune‐related and inflammatory disorders. John Wiley and Sons Inc. 2020-02-19 2020-04-03 /pmc/articles/PMC7132182/ /pubmed/32073750 http://dx.doi.org/10.15252/embr.201948925 Text en © 2020 The Authors. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Reports Fernández‐Messina, Lola Rodríguez‐Galán, Ana de Yébenes, Virginia G Gutiérrez‐Vázquez, Cristina Tenreiro, Sandra Seabra, Miguel C Ramiro, Almudena R Sánchez‐Madrid, Francisco Transfer of extracellular vesicle‐microRNA controls germinal center reaction and antibody production |
title | Transfer of extracellular vesicle‐microRNA controls germinal center reaction and antibody production |
title_full | Transfer of extracellular vesicle‐microRNA controls germinal center reaction and antibody production |
title_fullStr | Transfer of extracellular vesicle‐microRNA controls germinal center reaction and antibody production |
title_full_unstemmed | Transfer of extracellular vesicle‐microRNA controls germinal center reaction and antibody production |
title_short | Transfer of extracellular vesicle‐microRNA controls germinal center reaction and antibody production |
title_sort | transfer of extracellular vesicle‐microrna controls germinal center reaction and antibody production |
topic | Reports |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7132182/ https://www.ncbi.nlm.nih.gov/pubmed/32073750 http://dx.doi.org/10.15252/embr.201948925 |
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