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Vitamin A treatment rescues neonatal infection-induced durably impaired lymph node function (scRNA-Seq)

ABSTRACT: Gut-draining mesenteric and celiac lymph nodes (mLNs and celLNs) critically contribute to peripheral tolerance towards food and microbial antigens by efficiently 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. In the present study, we demonstrated that a transient neonatal gastrointestinal infection long-lastingly affects the functionality of celLN by permanently abrogating the efficient Treg-inducing capacity of celLN SCs. The neonatal infections durably shifted the heterogeneity of celLN SCs with permanently altered expression of genes involved in chemotaxis and inflammatory responses, resulting in a lastingly skewed dendritic cell (DC) composition. Mechanistically, transiently reduced VA levels caused the long-lastingly impaired celLN function, which could be rescued by an early-life VA supplementation. Together, our data highlight the therapeutic potential of VA treatment post gastrointestinal infections in infants.

ORGANISM(S): Mus musculus

PROVIDER: GSE183390 | GEO | 2023/12/31

REPOSITORIES: GEO

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