TY - JOUR

T1 - 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

AU - Zakariassen, Hannah Louise

AU - Bendtsen, Katja Maria

AU - Tougaard, Peter

AU - Hansen, Axel Kornerup

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - cytotoxic T cells

KW - gut microbiota

KW - helper T cells

KW - regulatory T cells

KW - thymocytes

U2 - 10.1177/2058739218823466

DO - 10.1177/2058739218823466

M3 - Journal article

VL - 17

SP - 1

EP - 16

JO - European Journal of Inflammation

JF - European Journal of Inflammation

SN - 1721-727X

ER -