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The circadian clock Period 2 gene regulates gamma interferon production of NK cells in host response to lipopolysaccharide-induced endotoxic shock
Liu, Jianguo; Mankani, Guantham; Shi, Xiaoyan; Meyer, Mark; Cunningham-Runddles, Susana; Ma, Xiaojing; Sun, Zhong Sheng; Z. S. Sun
2006-08-01
Source PublicationINFECTION AND IMMUNITY
ISSN0019-9567
SubtypeArticle
Volume74Issue:8Pages:4750-4756
AbstractThe Period 2 (Per2) gene is a key molecular component in controlling mammalian circadian rhythms at the levels of gene expression, physiology, and pathogenesis. Although many immune parameters, such as the number of different subtypes of circulating immune cells and the level of cytokine production in response to infection with bacteria and viruses, have been well documented to display a circadian pattern in mammals, the basic features of molecular clock components in the immune system and the role of clock genes in regulating host immune defenses remain uncharacterized. Previously, we have reported that circadian clock genes oscillate in human mononuclear cells. Here we report that Per2-deficient mice were more resistant to lipopolysaccharide (LPS)-induced endotoxic shock than control wild-type mice. We further demonstrate that the levels of the proinflammatory cytokines gamma interferon (IFN-gamma) and interleukin-1 beta (IL-1 beta) in the serum were dramatically decreased in Per2(-/-) mice following LPS challenge, while production of tumor necrosis factor alpha, IL-6, and IL-10 was approximately normal, compared to that in control wild-type mice. Flow cytometric analyses confirmed that the cellularity of most of the immune cell subs/-) mice was attributable to defective NK and NKT cell function. Our data suggest that Per2 is an important regulator of NK cell function, therefore providing the first direct link between the circadian clock system and innate immune responses.; The Period 2 (Per2) gene is a key molecular component in controlling mammalian circadian rhythms at the levels of gene expression, physiology, and pathogenesis. Although many immune parameters, such as the number of different subtypes of circulating immune cells and the level of cytokine production in response to infection with bacteria and viruses, have been well documented to display a circadian pattern in mammals, the basic features of molecular clock components in the immune system and the role of clock genes in regulating host immune defenses remain uncharacterized. Previously, we have reported that circadian clock genes oscillate in human mononuclear cells. Here we report that Per2-deficient mice were more resistant to lipopolysaccharide (LPS)-induced endotoxic shock than control wild-type mice. We further demonstrate that the levels of the proinflammatory cytokines gamma interferon (IFN-gamma) and interleukin-1 beta (IL-1 beta) in the serum were dramatically decreased in Per2(-/-) mice following LPS challenge, while production of tumor necrosis factor alpha, IL-6, and IL-10 was approximately normal, compared to that in control wild-type mice. Flow cytometric analyses confirmed that the cellularity of most of the immune cell subsets in the spleens of LPS-challenged mice was normal and that the impaired IFN-gamma production in Per2(-/-) mice was attributable to defective NK and NKT cell function. Our data suggest that Per2 is an important regulator of NK cell function, therefore providing the first direct link between the circadian clock system and innate immune responses.
Subject Area分子生物学
Indexed BySCI
Language英语
WOS IDWOS:000239381400040
Citation statistics
Cited Times:118[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.psych.ac.cn/handle/311026/5741
Collection中国科学院心理研究所回溯数据库(1956-2010)
Corresponding AuthorZ. S. Sun
Affiliation1.Cornell Univ, Weill Med Coll, Dept Pediat, New York, NY 10021 USA
2.Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, New York, NY 10021 USA
3.Chinese Acad Sci, Inst Psychol, Behav Genet Ctr, Beijing 100101, Peoples R China
Recommended Citation
GB/T 7714
Liu, Jianguo,Mankani, Guantham,Shi, Xiaoyan,et al. The circadian clock Period 2 gene regulates gamma interferon production of NK cells in host response to lipopolysaccharide-induced endotoxic shock[J]. INFECTION AND IMMUNITY,2006,74(8):4750-4756.
APA Liu, Jianguo.,Mankani, Guantham.,Shi, Xiaoyan.,Meyer, Mark.,Cunningham-Runddles, Susana.,...&Z. S. Sun.(2006).The circadian clock Period 2 gene regulates gamma interferon production of NK cells in host response to lipopolysaccharide-induced endotoxic shock.INFECTION AND IMMUNITY,74(8),4750-4756.
MLA Liu, Jianguo,et al."The circadian clock Period 2 gene regulates gamma interferon production of NK cells in host response to lipopolysaccharide-induced endotoxic shock".INFECTION AND IMMUNITY 74.8(2006):4750-4756.
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