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

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. Single cell RNA-seq on FACS-isolated CD45-CD24-celiac lymph node stromal cells of PBS-treated and Yersinia-treated mice