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Butyrate induced Tregs are capable of migration from the GALT to the pancreas to restore immunological tolerance during type-1 diabetes
Type-1 diabetes (T1D) is an autoimmune disease caused by progressive loss of insulin-producing beta cells in the pancreas. Butyrate is a commensal microbial-derived metabolite, implicated in intestinal homeostasis and immune regulation. Here, we investigated the mechanism of diabetes remission in no...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644709/ https://www.ncbi.nlm.nih.gov/pubmed/33154424 http://dx.doi.org/10.1038/s41598-020-76109-y |
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author | Jacob, Neenu Jaiswal, Shivani Maheshwari, Deep Nallabelli, Nayudu Khatri, Neeraj Bhatia, Alka Bal, Amanjit Malik, Vivek Verma, Savita Kumar, Rakesh Sachdeva, Naresh |
author_facet | Jacob, Neenu Jaiswal, Shivani Maheshwari, Deep Nallabelli, Nayudu Khatri, Neeraj Bhatia, Alka Bal, Amanjit Malik, Vivek Verma, Savita Kumar, Rakesh Sachdeva, Naresh |
author_sort | Jacob, Neenu |
collection | PubMed |
description | Type-1 diabetes (T1D) is an autoimmune disease caused by progressive loss of insulin-producing beta cells in the pancreas. Butyrate is a commensal microbial-derived metabolite, implicated in intestinal homeostasis and immune regulation. Here, we investigated the mechanism of diabetes remission in non-obese diabetic (NOD) mice following butyrate administration. Sodium butyrate (150 mM) was administered to female NOD mice in drinking water after the onset of hyperglycemia (15–25 weeks age) and at 4 weeks of age (early-intervention group). Butyrate administration reduced the progression of hyperglycemia in diabetic mice and delayed onset of diabetes in the early-intervention group with a reduction in insulitis. Butyrate administration increased regulatory T cells (Tregs) in the colon, mesenteric lymph nodes, Peyer’s patches, and its protective effects diminished upon depletion of Tregs. Further, an increase in α4β7, CCR9, and GPR15 expressing Tregs in the pancreatic lymph nodes (PLN) and pancreas in butyrate-treated mice suggested migration of gut-primed Tregs towards the pancreas. Finally, the adoptive transfer experiments demonstrated that induced Tregs from gut-associated lymphoid tissue can migrate towards the pancreas and PLN and delay the onset of diabetes. Our results thus suggest that early administration of butyrate can restore immunological tolerance during T1D via induction of Tregs with migratory capabilities. |
format | Online Article Text |
id | pubmed-7644709 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-76447092020-11-06 Butyrate induced Tregs are capable of migration from the GALT to the pancreas to restore immunological tolerance during type-1 diabetes Jacob, Neenu Jaiswal, Shivani Maheshwari, Deep Nallabelli, Nayudu Khatri, Neeraj Bhatia, Alka Bal, Amanjit Malik, Vivek Verma, Savita Kumar, Rakesh Sachdeva, Naresh Sci Rep Article Type-1 diabetes (T1D) is an autoimmune disease caused by progressive loss of insulin-producing beta cells in the pancreas. Butyrate is a commensal microbial-derived metabolite, implicated in intestinal homeostasis and immune regulation. Here, we investigated the mechanism of diabetes remission in non-obese diabetic (NOD) mice following butyrate administration. Sodium butyrate (150 mM) was administered to female NOD mice in drinking water after the onset of hyperglycemia (15–25 weeks age) and at 4 weeks of age (early-intervention group). Butyrate administration reduced the progression of hyperglycemia in diabetic mice and delayed onset of diabetes in the early-intervention group with a reduction in insulitis. Butyrate administration increased regulatory T cells (Tregs) in the colon, mesenteric lymph nodes, Peyer’s patches, and its protective effects diminished upon depletion of Tregs. Further, an increase in α4β7, CCR9, and GPR15 expressing Tregs in the pancreatic lymph nodes (PLN) and pancreas in butyrate-treated mice suggested migration of gut-primed Tregs towards the pancreas. Finally, the adoptive transfer experiments demonstrated that induced Tregs from gut-associated lymphoid tissue can migrate towards the pancreas and PLN and delay the onset of diabetes. Our results thus suggest that early administration of butyrate can restore immunological tolerance during T1D via induction of Tregs with migratory capabilities. Nature Publishing Group UK 2020-11-05 /pmc/articles/PMC7644709/ /pubmed/33154424 http://dx.doi.org/10.1038/s41598-020-76109-y Text en © The Author(s) 2020 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/. |
spellingShingle | Article Jacob, Neenu Jaiswal, Shivani Maheshwari, Deep Nallabelli, Nayudu Khatri, Neeraj Bhatia, Alka Bal, Amanjit Malik, Vivek Verma, Savita Kumar, Rakesh Sachdeva, Naresh Butyrate induced Tregs are capable of migration from the GALT to the pancreas to restore immunological tolerance during type-1 diabetes |
title | Butyrate induced Tregs are capable of migration from the GALT to the pancreas to restore immunological tolerance during type-1 diabetes |
title_full | Butyrate induced Tregs are capable of migration from the GALT to the pancreas to restore immunological tolerance during type-1 diabetes |
title_fullStr | Butyrate induced Tregs are capable of migration from the GALT to the pancreas to restore immunological tolerance during type-1 diabetes |
title_full_unstemmed | Butyrate induced Tregs are capable of migration from the GALT to the pancreas to restore immunological tolerance during type-1 diabetes |
title_short | Butyrate induced Tregs are capable of migration from the GALT to the pancreas to restore immunological tolerance during type-1 diabetes |
title_sort | butyrate induced tregs are capable of migration from the galt to the pancreas to restore immunological tolerance during type-1 diabetes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644709/ https://www.ncbi.nlm.nih.gov/pubmed/33154424 http://dx.doi.org/10.1038/s41598-020-76109-y |
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