Cargando…
Pharmacological Enhancement of Regeneration-Dependent Regulatory T Cell Recruitment in Zebrafish
Regenerative capacity varies greatly between species. Mammals are limited in their ability to regenerate damaged cells, tissues and organs compared to organisms with robust regenerative responses, such as zebrafish. The regeneration of zebrafish tissues including the heart, spinal cord and retina re...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834363/ https://www.ncbi.nlm.nih.gov/pubmed/31635133 http://dx.doi.org/10.3390/ijms20205189 |
_version_ | 1783466472848228352 |
---|---|
author | Zwi, Stephanie F. Choron, Clarisse Zheng, Dawei Nguyen, David Zhang, Yuxi Roshal, Camilla Kikuchi, Kazu Hesselson, Daniel |
author_facet | Zwi, Stephanie F. Choron, Clarisse Zheng, Dawei Nguyen, David Zhang, Yuxi Roshal, Camilla Kikuchi, Kazu Hesselson, Daniel |
author_sort | Zwi, Stephanie F. |
collection | PubMed |
description | Regenerative capacity varies greatly between species. Mammals are limited in their ability to regenerate damaged cells, tissues and organs compared to organisms with robust regenerative responses, such as zebrafish. The regeneration of zebrafish tissues including the heart, spinal cord and retina requires foxp3a+ zebrafish regulatory T cells (zTregs). However, it remains unclear whether the muted regenerative responses in mammals are due to impaired recruitment and/or function of homologous mammalian regulatory T cell (Treg) populations. Here, we explore the possibility of enhancing zTreg recruitment with pharmacological interventions using the well-characterized zebrafish tail amputation model to establish a high-throughput screening platform. Injury-infiltrating zTregs were transgenically labelled to enable rapid quantification in live animals. We screened the NIH Clinical Collection (727 small molecules) for modulators of zTreg recruitment to the regenerating tissue at three days post-injury. We discovered that the dopamine agonist pramipexole, a drug currently approved for treating Parkinson’s Disease, specifically enhanced zTreg recruitment after injury. The dopamine antagonist SCH-23390 blocked pramipexole activity, suggesting that peripheral dopaminergic signaling may regulate zTreg recruitment. Similar pharmacological approaches for enhancing mammalian Treg recruitment may be an important step in developing novel strategies for tissue regeneration in humans. |
format | Online Article Text |
id | pubmed-6834363 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-68343632019-11-25 Pharmacological Enhancement of Regeneration-Dependent Regulatory T Cell Recruitment in Zebrafish Zwi, Stephanie F. Choron, Clarisse Zheng, Dawei Nguyen, David Zhang, Yuxi Roshal, Camilla Kikuchi, Kazu Hesselson, Daniel Int J Mol Sci Article Regenerative capacity varies greatly between species. Mammals are limited in their ability to regenerate damaged cells, tissues and organs compared to organisms with robust regenerative responses, such as zebrafish. The regeneration of zebrafish tissues including the heart, spinal cord and retina requires foxp3a+ zebrafish regulatory T cells (zTregs). However, it remains unclear whether the muted regenerative responses in mammals are due to impaired recruitment and/or function of homologous mammalian regulatory T cell (Treg) populations. Here, we explore the possibility of enhancing zTreg recruitment with pharmacological interventions using the well-characterized zebrafish tail amputation model to establish a high-throughput screening platform. Injury-infiltrating zTregs were transgenically labelled to enable rapid quantification in live animals. We screened the NIH Clinical Collection (727 small molecules) for modulators of zTreg recruitment to the regenerating tissue at three days post-injury. We discovered that the dopamine agonist pramipexole, a drug currently approved for treating Parkinson’s Disease, specifically enhanced zTreg recruitment after injury. The dopamine antagonist SCH-23390 blocked pramipexole activity, suggesting that peripheral dopaminergic signaling may regulate zTreg recruitment. Similar pharmacological approaches for enhancing mammalian Treg recruitment may be an important step in developing novel strategies for tissue regeneration in humans. MDPI 2019-10-19 /pmc/articles/PMC6834363/ /pubmed/31635133 http://dx.doi.org/10.3390/ijms20205189 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Zwi, Stephanie F. Choron, Clarisse Zheng, Dawei Nguyen, David Zhang, Yuxi Roshal, Camilla Kikuchi, Kazu Hesselson, Daniel Pharmacological Enhancement of Regeneration-Dependent Regulatory T Cell Recruitment in Zebrafish |
title | Pharmacological Enhancement of Regeneration-Dependent Regulatory T Cell Recruitment in Zebrafish |
title_full | Pharmacological Enhancement of Regeneration-Dependent Regulatory T Cell Recruitment in Zebrafish |
title_fullStr | Pharmacological Enhancement of Regeneration-Dependent Regulatory T Cell Recruitment in Zebrafish |
title_full_unstemmed | Pharmacological Enhancement of Regeneration-Dependent Regulatory T Cell Recruitment in Zebrafish |
title_short | Pharmacological Enhancement of Regeneration-Dependent Regulatory T Cell Recruitment in Zebrafish |
title_sort | pharmacological enhancement of regeneration-dependent regulatory t cell recruitment in zebrafish |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834363/ https://www.ncbi.nlm.nih.gov/pubmed/31635133 http://dx.doi.org/10.3390/ijms20205189 |
work_keys_str_mv | AT zwistephanief pharmacologicalenhancementofregenerationdependentregulatorytcellrecruitmentinzebrafish AT choronclarisse pharmacologicalenhancementofregenerationdependentregulatorytcellrecruitmentinzebrafish AT zhengdawei pharmacologicalenhancementofregenerationdependentregulatorytcellrecruitmentinzebrafish AT nguyendavid pharmacologicalenhancementofregenerationdependentregulatorytcellrecruitmentinzebrafish AT zhangyuxi pharmacologicalenhancementofregenerationdependentregulatorytcellrecruitmentinzebrafish AT roshalcamilla pharmacologicalenhancementofregenerationdependentregulatorytcellrecruitmentinzebrafish AT kikuchikazu pharmacologicalenhancementofregenerationdependentregulatorytcellrecruitmentinzebrafish AT hesselsondaniel pharmacologicalenhancementofregenerationdependentregulatorytcellrecruitmentinzebrafish |