Early-life vitamin A treatment rescues neonatal infection-induced durably impaired tolerogenic properties of celiac lymph nodes.
Cell Rep
; 43(5): 114153, 2024 May 28.
Article
in En
| MEDLINE
| ID: mdl-38687643
ABSTRACT
Gut-draining mesenteric and celiac lymph nodes (mLNs and celLNs) critically contribute to peripheral tolerance toward food and microbial antigens by supporting the de novo induction of regulatory T cells (Tregs). These tolerogenic properties of mLNs and celLNs are stably imprinted within stromal cells (SCs) by microbial signals and vitamin A (VA), respectively. Here, we report that a single, transient gastrointestinal infection in the neonatal, but not adult, period durably abrogates the efficient Treg-inducing capacity of celLNs by altering the subset composition and gene expression profile of celLNSCs. These cells carry information about the early-life pathogen encounter until adulthood and durably instruct migratory dendritic cells entering the celLN with reduced tolerogenic properties. Mechanistically, transiently reduced VA levels cause long-lasting celLN functional impairment, which can be rescued by early-life treatment with VA. Together, our data highlight the therapeutic potential of VA to prevent sequelae post gastrointestinal infections in infants.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Vitamin A
/
T-Lymphocytes, Regulatory
/
Lymph Nodes
Limits:
Animals
Language:
En
Journal:
Cell Rep
Year:
2024
Type:
Article
Affiliation country:
Germany