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Neonatal liver niches program T cell tolerance.

Eva-Lena Stange1, Trong-Hieu Nguyen2, Dustyn Mendoza3

  • 1Institute of Medical Microbiology, University Hospital RWTH Aachen; Aachen, Germany.

Biorxiv : the Preprint Server for Biology
|February 6, 2026
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Summary
This summary is machine-generated.

The neonatal liver expands regulatory T cells (Tregs) independently of gut microbes, establishing immune tolerance. This early immune education impacts viral infections and liver disease later in life.

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Area of Science:

  • Immunology
  • Hepatology
  • Developmental Biology

Background:

  • The immune system must balance tolerance to self and commensals with pathogen defense after birth.
  • The liver's role in early immune development and tolerance is not fully understood.

Purpose of the Study:

  • To investigate the neonatal liver's function as a hub for immune system education.
  • To elucidate the mechanisms governing T cell populations in the early postnatal liver.

Main Methods:

  • Characterization of T cell populations (Tregs and Tconvs) in the neonatal liver.
  • Analysis of dendritic cell (DC) subsets (cDC1s) and their interactions with T cells.
  • Investigation of molecular pathways including MHCII, CCR7, and PD-L1.

Main Results:

  • A microbiota-independent expansion of regulatory T cells (Tregs) occurs in the neonatal liver (weeks 1-2).
  • CCR7+ cDC1s present antigens via MHCII, forming tolerogenic DC:T cell clusters that promote Treg expansion.
  • PD-L1 checkpoints selectively increase Tregs without activating conventional T cells (Tconvs).
  • This neonatal program influences susceptibility to chronic viral infections and protects against steatotic disease in adulthood.

Conclusions:

  • The neonatal liver acts as a critical site for early T cell education and immune tolerance.
  • The described transient program has significant, timing-sensitive implications for early-life interventions and disease susceptibility.