Zou, ManggePezoldt, JoernMohr, JulianePhilipsen, LarsLeufgen, AndreaCerovic, VukWiechers, CarolinPils, MarinaOrtiz, DiegoHao, LianxuYang, JuhaoBeckstette, MichaelDupont, AlineHornef, MathiasDersch, PetraStrowig, TillMuller, Andreas J.Raila, JensHuehn, Jochen2024-06-192024-06-192024-06-192024-05-2810.1016/j.celrep.2024.114153https://infoscience.epfl.ch/handle/20.500.14299/208720WOS:001236989500001Gut -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.Life Sciences & BiomedicineStromal CellsDendritic CellsOral ToleranceInductionLiverCampylobacterSalmonellaGenerationYersiniaImmunitytext::journal::journal article::research article