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Cell Mol Immunol. 2019 Jun 6. doi: 10.1038/s41423-019-0246-9. [Epub ahead of print]

A wave of Foxp3+ regulatory T cell accumulation in the neonatal liver plays unique roles in maintaining self-tolerance.

Author information

1
Department of Immunology, School of Basic Medical Sciences, NHC Key Laboratory of Medical Immunology, Peking University, Beijing, China.
2
Center for Molecular Metabolism, Nanjing University of Science & Technology, No. 364 Building, 200 Xiaolinwei Street, Nanjing, 210094, China.
3
Pediatric Diabetes Research Center, Department of Pediatrics, UCSD, La Jolla, CA, USA.
4
Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
5
Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University People's Hospital & Institute of Hematology, Beijing, 100044, China.
6
Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.
7
Peking University Medical and Health Analytical Center, Peking University, Beijing, 100191, China. wuhounan@bjmu.edu.cn.
8
Translational Stem Cell Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China. mart555@163.com.
9
Department of Immunology, School of Basic Medical Sciences, NHC Key Laboratory of Medical Immunology, Peking University, Beijing, China. qingge@bjmu.edu.cn.
10
Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, 100191, China. qingge@bjmu.edu.cn.

Abstract

Newborn animals require tightly regulated local and systemic immune environments to govern the development and maturation of multiple organs/tissues even though the immune system itself is far from mature during the neonatal period. Regulatory T cells (Tregs) are essential for maintaining immune tolerance/homeostasis and modulating inflammatory responses. The features of Tregs in the neonatal liver under steady-state conditions are not well understood. The present study aimed to investigate the phenotype, functions, and significance of neonatal Tregs in the liver. We found a wave of thymus-derived Treg influx into the liver during 1-2 weeks of age. Depletion of these Tregs between days 7 and 11 after birth rapidly resulted in Th1-type liver inflammation and metabolic disorder. More Tregs in the neonatal liver than in the spleen underwent MHC II-dependent activation and proliferation, and the liver Tregs acquired stronger suppressive functions. The transcriptomic profile of these neonatal liver Tregs showed elevated expression of PPARĪ³ and T-bet and features of Tregs that utilize lipid metabolic machinery and are capable of regulating Th1 responses. The accumulation of Tregs with unique features in the neonatal liver is critical to ensure self-tolerance and liver maturation.

KEYWORDS:

Foxp3; Neonatal period,; Th1-type inflammation; Treg cells; liver

PMID:
31171863
DOI:
10.1038/s41423-019-0246-9

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