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Local IL-10 delivery modulates the immune response and enhances repair of volumetric muscle loss muscle injury

This study was designed to test the hypothesis that in addition to repairing the architectural and cellular cues via regenerative medicine, the delivery of immune cues (immunotherapy) may be needed to enhance regeneration following volumetric muscle loss (VML) injury. We identified IL-10 signaling a...

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Autores principales: Huynh, Tai, Reed, Cassandra, Blackwell, Zain, Phelps, Payton, Herrera, Luis C. Pinzon, Almodovar, Jorge, Zaharoff, David A., Wolchok, Jeffrey
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9898301/
https://www.ncbi.nlm.nih.gov/pubmed/36737628
http://dx.doi.org/10.1038/s41598-023-27981-x
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author Huynh, Tai
Reed, Cassandra
Blackwell, Zain
Phelps, Payton
Herrera, Luis C. Pinzon
Almodovar, Jorge
Zaharoff, David A.
Wolchok, Jeffrey
author_facet Huynh, Tai
Reed, Cassandra
Blackwell, Zain
Phelps, Payton
Herrera, Luis C. Pinzon
Almodovar, Jorge
Zaharoff, David A.
Wolchok, Jeffrey
author_sort Huynh, Tai
collection PubMed
description This study was designed to test the hypothesis that in addition to repairing the architectural and cellular cues via regenerative medicine, the delivery of immune cues (immunotherapy) may be needed to enhance regeneration following volumetric muscle loss (VML) injury. We identified IL-10 signaling as a promising immunotherapeutic target. To explore the impact of targeting IL-10 signaling, tibialis anterior (TA) VML injuries were created and then treated in rats using autologous minced muscle (MM). Animals received either recombinant rat IL-10 or phosphate buffered saline (PBS) controls injections at the site of VML repair beginning 7 days post injury (DPI) and continuing every other day (4 injections total) until 14 DPI. At 56 DPI (study endpoint), significant improvements to TA contractile torque (82% of uninjured values & 170% of PBS values), TA mass, and myofiber size in response to IL-10 treatment were detected. Whole transcriptome analysis at 14 DPI revealed activation of IL-10 signaling, muscle hypertrophy, and lymphocytes signaling pathways. Expression of ST2, a regulatory T (T(reg)) cell receptor, was dramatically increased at the VML repair site in response to IL-10 treatment when compared to PBS controls. The findings suggest that the positive effect of delayed IL-10 delivery might be due to immuno-suppressive T(reg) cell recruitment.
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spelling pubmed-98983012023-02-05 Local IL-10 delivery modulates the immune response and enhances repair of volumetric muscle loss muscle injury Huynh, Tai Reed, Cassandra Blackwell, Zain Phelps, Payton Herrera, Luis C. Pinzon Almodovar, Jorge Zaharoff, David A. Wolchok, Jeffrey Sci Rep Article This study was designed to test the hypothesis that in addition to repairing the architectural and cellular cues via regenerative medicine, the delivery of immune cues (immunotherapy) may be needed to enhance regeneration following volumetric muscle loss (VML) injury. We identified IL-10 signaling as a promising immunotherapeutic target. To explore the impact of targeting IL-10 signaling, tibialis anterior (TA) VML injuries were created and then treated in rats using autologous minced muscle (MM). Animals received either recombinant rat IL-10 or phosphate buffered saline (PBS) controls injections at the site of VML repair beginning 7 days post injury (DPI) and continuing every other day (4 injections total) until 14 DPI. At 56 DPI (study endpoint), significant improvements to TA contractile torque (82% of uninjured values & 170% of PBS values), TA mass, and myofiber size in response to IL-10 treatment were detected. Whole transcriptome analysis at 14 DPI revealed activation of IL-10 signaling, muscle hypertrophy, and lymphocytes signaling pathways. Expression of ST2, a regulatory T (T(reg)) cell receptor, was dramatically increased at the VML repair site in response to IL-10 treatment when compared to PBS controls. The findings suggest that the positive effect of delayed IL-10 delivery might be due to immuno-suppressive T(reg) cell recruitment. Nature Publishing Group UK 2023-02-03 /pmc/articles/PMC9898301/ /pubmed/36737628 http://dx.doi.org/10.1038/s41598-023-27981-x Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Huynh, Tai
Reed, Cassandra
Blackwell, Zain
Phelps, Payton
Herrera, Luis C. Pinzon
Almodovar, Jorge
Zaharoff, David A.
Wolchok, Jeffrey
Local IL-10 delivery modulates the immune response and enhances repair of volumetric muscle loss muscle injury
title Local IL-10 delivery modulates the immune response and enhances repair of volumetric muscle loss muscle injury
title_full Local IL-10 delivery modulates the immune response and enhances repair of volumetric muscle loss muscle injury
title_fullStr Local IL-10 delivery modulates the immune response and enhances repair of volumetric muscle loss muscle injury
title_full_unstemmed Local IL-10 delivery modulates the immune response and enhances repair of volumetric muscle loss muscle injury
title_short Local IL-10 delivery modulates the immune response and enhances repair of volumetric muscle loss muscle injury
title_sort local il-10 delivery modulates the immune response and enhances repair of volumetric muscle loss muscle injury
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9898301/
https://www.ncbi.nlm.nih.gov/pubmed/36737628
http://dx.doi.org/10.1038/s41598-023-27981-x
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