Abstract
Abstract Newborn animals require a tightly-regulated local and systemic immune environment to govern the development and maturation of multiple organs/tissues even when the immune system itself is far from mature during neonatal period. The regulatory T cells (Tregs) are essential in maintaining immune tolerance/homeostasis and modulating inflammatory responses. The features of Tregs in neonatal liver under steady state are not well understood. To investigate the phenotype, functions, and significance of neonatal Tregs in the liver, we compared the frequency, surface markers, functions, and transcriptome of liver and splenic Tregs in neonatal mice. We found a wave of thymus-derived Treg influx into the liver during the first 1–2-week age window. Depletion of these Tregs between days 7 and 11 after birth rapidly resulted in Th1-type autoimmune hepatitis and metabolic disorder. Compared to splenic Tregs, more Tregs in neonatal liver underwent MHC II-dependent activation and proliferation and acquired higher suppressive functions. The transcriptome profile of these neonatal liver Tregs showed elevated expression of Tbx21, Pparg, and features of Tregs capable of regulating Th1 responses and metabolic homeostasis. These results suggest that neonates have a transient accumulation of Tregs with unique features in the liver. This Treg influx is critical to ensure self-tolerance and liver maturation.
Published Version
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