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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Main Authors: Hannah Louise Zakariassen, Katja Maria Bendtsen, Peter Tougaard, Axel Kornerup Hansen
Format: Article
Language:English
Published: SAGE Publishing 2019-01-01
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.
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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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