Reduced early life mucosal integrity decreases thymic cell counts and increases local, but not thymic regulatory, T cell recruitment: Gut mucosal integrity breach and thymic T cells
Early life immune gut microbiota contact is critical for regulatory T cell–mediated oral tolerance induction. We induced a mucosal integrity breach with low dextran sulfate sodium dose right after weaning in BALB/c mice along with a standard high dose to study the impact of increased gut microbiota...
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Format: | Article |
Language: | English |
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SAGE Publishing
2019-01-01
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Series: | European Journal of Inflammation |
Online Access: | https://doi.org/10.1177/2058739218823466 |
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author | Hannah Louise Zakariassen Katja Maria Bendtsen Peter Tougaard Axel Kornerup Hansen |
author_facet | Hannah Louise Zakariassen Katja Maria Bendtsen Peter Tougaard Axel Kornerup Hansen |
author_sort | Hannah Louise Zakariassen |
collection | DOAJ |
description | Early life immune gut microbiota contact is critical for regulatory T cell–mediated oral tolerance induction. We induced a mucosal integrity breach with low dextran sulfate sodium dose right after weaning in BALB/c mice along with a standard high dose to study the impact of increased gut microbiota lymphatic tissue contact on the thymus. Both doses increased gut permeability, which caused a short-term generalized thymic involution and regulatory T cell induction in the mesenteric lymph nodes, even in the absence of clinically apparent inflammation in the low-dose group. The thymic regulatory T cells resisted thymic involution. In the low-dose group, we found acutely altered gut mobilization patterns characterized by changed gut-homing marker CD103 expression on mesenteric lymph node CD4 + T cells as well as on mature CD8 + T cells and developing CD4 − /CD8 − thymocytes. Furthermore, CD218a (IL-18-receptor-a) expression was acutely decreased on both mature CD8 + T cells and regulatory T cells, while increased on the mesenteric lymph node CD8 + T cells, indicating a direct link between the thymus and the mesenteric lymph nodes with CD218a in a functional role in thymic involution. Acute and non-persisting regulatory responses in the mesenteric lymph nodes were induced in the form of a relative regulatory T cell increase. We saw no changes in total thymic regulatory T cells and thus the thymus does not seem to play a major role of in the regulatory immunity induced by increased gut microbiota lymphatic tissue contact around weaning, which in our study primarily was located to the gut. |
first_indexed | 2024-12-21T11:33:02Z |
format | Article |
id | doaj.art-51b369186cdc406c9ccad1ba7cd73007 |
institution | Directory Open Access Journal |
issn | 2058-7392 |
language | English |
last_indexed | 2024-12-21T11:33:02Z |
publishDate | 2019-01-01 |
publisher | SAGE Publishing |
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series | European Journal of Inflammation |
spelling | doaj.art-51b369186cdc406c9ccad1ba7cd730072022-12-21T19:05:30ZengSAGE PublishingEuropean Journal of Inflammation2058-73922019-01-011710.1177/2058739218823466Reduced early life mucosal integrity decreases thymic cell counts and increases local, but not thymic regulatory, T cell recruitment: Gut mucosal integrity breach and thymic T cellsHannah Louise ZakariassenKatja Maria BendtsenPeter TougaardAxel Kornerup HansenEarly life immune gut microbiota contact is critical for regulatory T cell–mediated oral tolerance induction. We induced a mucosal integrity breach with low dextran sulfate sodium dose right after weaning in BALB/c mice along with a standard high dose to study the impact of increased gut microbiota lymphatic tissue contact on the thymus. Both doses increased gut permeability, which caused a short-term generalized thymic involution and regulatory T cell induction in the mesenteric lymph nodes, even in the absence of clinically apparent inflammation in the low-dose group. The thymic regulatory T cells resisted thymic involution. In the low-dose group, we found acutely altered gut mobilization patterns characterized by changed gut-homing marker CD103 expression on mesenteric lymph node CD4 + T cells as well as on mature CD8 + T cells and developing CD4 − /CD8 − thymocytes. Furthermore, CD218a (IL-18-receptor-a) expression was acutely decreased on both mature CD8 + T cells and regulatory T cells, while increased on the mesenteric lymph node CD8 + T cells, indicating a direct link between the thymus and the mesenteric lymph nodes with CD218a in a functional role in thymic involution. Acute and non-persisting regulatory responses in the mesenteric lymph nodes were induced in the form of a relative regulatory T cell increase. We saw no changes in total thymic regulatory T cells and thus the thymus does not seem to play a major role of in the regulatory immunity induced by increased gut microbiota lymphatic tissue contact around weaning, which in our study primarily was located to the gut.https://doi.org/10.1177/2058739218823466 |
spellingShingle | Hannah Louise Zakariassen Katja Maria Bendtsen Peter Tougaard Axel Kornerup Hansen Reduced early life mucosal integrity decreases thymic cell counts and increases local, but not thymic regulatory, T cell recruitment: Gut mucosal integrity breach and thymic T cells European Journal of Inflammation |
title | Reduced early life mucosal integrity decreases thymic cell counts and increases local, but not thymic regulatory, T cell recruitment: Gut mucosal integrity breach and thymic T cells |
title_full | Reduced early life mucosal integrity decreases thymic cell counts and increases local, but not thymic regulatory, T cell recruitment: Gut mucosal integrity breach and thymic T cells |
title_fullStr | Reduced early life mucosal integrity decreases thymic cell counts and increases local, but not thymic regulatory, T cell recruitment: Gut mucosal integrity breach and thymic T cells |
title_full_unstemmed | Reduced early life mucosal integrity decreases thymic cell counts and increases local, but not thymic regulatory, T cell recruitment: Gut mucosal integrity breach and thymic T cells |
title_short | Reduced early life mucosal integrity decreases thymic cell counts and increases local, but not thymic regulatory, T cell recruitment: Gut mucosal integrity breach and thymic T cells |
title_sort | reduced early life mucosal integrity decreases thymic cell counts and increases local but not thymic regulatory t cell recruitment gut mucosal integrity breach and thymic t cells |
url | https://doi.org/10.1177/2058739218823466 |
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