气候变化领域集成服务门户(CCPortal): FXR mediates T cell-intrinsic responses to reduced feeding during infection

CCPortal

DOI	10.1073/PNAS.2020619117
	FXR mediates T cell-intrinsic responses to reduced feeding during infection
	Campbell C.; Marchildon F.; Michaels A.J.; Takemoto N.; van der Veeken J.; Schizas M.; Pritykin Y.; Leslie C.S.; Intlekofer A.M.; Cohen P.; Rudensky A.Y.
发表日期	2021
ISSN	00278424
起始页码	33446
结束页码	33454
卷号	117 期号:52
英文摘要	Reduced nutrient intake is a widely conserved manifestation of sickness behavior with poorly characterized effects on adaptive immune responses. During infectious challenges, naive T cells encountering their cognate antigen become activated and differentiate into highly proliferative effector T cells. Despite their evident metabolic shift upon activation, it remains unclear how effector T cells respond to changes in nutrient availability in vivo. Here, we show that spontaneous or imposed feeding reduction during infection decreases the numbers of splenic lymphocytes. Effector T cells showed cell-intrinsic responses dependent on the nuclear receptor Farnesoid X Receptor (FXR). Deletion of FXR in T cells prevented starvation-induced loss of lymphocytes and increased effector T cell fitness in nutrient-limiting conditions, but imparted greater weight loss to the host. FXR deficiency increased the contribution of glutamine and fatty acids toward respiration and enhanced cell survival under low-glucose conditions. Provision of glucose during anorexia of infection rescued effector T cells, suggesting that this sugar is a limiting nutrient for activated lymphocytes and that alternative fuel usage may affect cell survival in starved animals. Altogether, we identified a mechanism by which the host scales immune responses according to food intake, featuring FXR as a T cell-intrinsic sensor. © 2020 National Academy of Sciences. All rights reserved.
英文关键词	Anorexia; FXR; Infection; T cells
语种	英语
scopus关键词	cell receptor; farnesoid X-activated receptor; animal; anorexia; C57BL mouse; diet restriction; feeding behavior; genetic transcription; immunology; lymphocytic choriomeningitis; Lymphocytic choriomeningitis virus; metabolism; pathology; physiology; spleen; T lymphocyte; virology; Animals; Anorexia; Fasting; Feeding Behavior; Lymphocytic Choriomeningitis; Lymphocytic choriomeningitis virus; Mice, Inbred C57BL; Nutrients; Receptors, Cytoplasmic and Nuclear; Spleen; T-Lymphocytes; Transcription, Genetic
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179655
作者单位	Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States; Laboratory of Molecular Metabolism, Rockefeller University, New York, NY 10065, United States; Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, New York, NY 10021, United States; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States; Computational and Systems Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States; Howard Hughes Medical Institute, Sloan Kettering Institute, New York, NY 10065, United States; Immunology Program, Ludwig Center, Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States
推荐引用方式 GB/T 7714	Campbell C.,Marchildon F.,Michaels A.J.,et al. FXR mediates T cell-intrinsic responses to reduced feeding during infection[J],2021,117(52).
APA	Campbell C..,Marchildon F..,Michaels A.J..,Takemoto N..,van der Veeken J..,...&Rudensky A.Y..(2021).FXR mediates T cell-intrinsic responses to reduced feeding during infection.Proceedings of the National Academy of Sciences of the United States of America,117(52).
MLA	Campbell C.,et al."FXR mediates T cell-intrinsic responses to reduced feeding during infection".Proceedings of the National Academy of Sciences of the United States of America 117.52(2021).