Impaired leukocyte trafficking and skin inflammatory responses in hamsters lacking a functional circadian system

被引:34
作者
Prendergast, Brian J. [1 ,2 ]
Cable, Erin J. [1 ]
Patel, Priyesh N. [1 ]
Pyter, Leah M. [1 ]
Onishi, Kenneth G. [1 ]
Stevenson, Tyler J. [1 ]
Ruby, Norman F. [3 ]
Bradley, Sean P. [1 ]
机构
[1] Univ Chicago, Dept Psychol, Chicago, IL 60637 USA
[2] Univ Chicago, Comm Neurobiol, Chicago, IL 60637 USA
[3] Stanford Univ, Dept Biol Sci, Palo Alto, CA 94305 USA
关键词
Leukocyte trafficking; Delayed-type hypersensitivity; Entrainment; SCN; Inflammation; LIGHT-DARK CYCLE; BEHAVIORAL TOLERANCE DEVELOPMENT; SUPRACHIASMATIC NUCLEUS; SIBERIAN HAMSTERS; GENE-EXPRESSION; CONTACT HYPERSENSITIVITY; DIURNAL-VARIATION; STRESS HORMONES; DENDRITIC CELLS; IMMUNE FUNCTION;
D O I
10.1016/j.bbi.2013.02.007
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The immune system is under strong circadian control, and circadian desynchrony is a risk factor for metabolic disorders, inflammatory responses and cancer. Signaling pathways that maintain circadian rhythms (CRs) in immune function in vivo, and the mechanisms by which circadian desynchrony impairs immune function, remain to be fully identified. These experiments tested the hypothesis that the hypothalamic circadian pacemaker in the suprachiasmatic nucleus (SCN) drives CRs in the immune system, using a non-invasive model of SCN circadian arrhythmia. Robust CRs in blood leukocyte trafficking, with a peak during the early light phase (ZT4) and nadir in the early dark phase (ZT18), were absent in arrhythmic hamsters, as were CRs in spleen clock gene (per1, bmal1) expression, indicating that a functional pacemaker in the SCN is required for the generation of CRs in leukocyte trafficking and for driving peripheral clocks in secondary lymphoid organs. Pinealectomy was without effect on CRs in leukocyte trafficking, but abolished CRs in spleen clock gene expression, indicating that nocturnal melatonin secretion is necessary for communicating circadian time information to the spleen. CRs in trafficking of antigen presenting cells (CD11c(+) dendritic cells) in the skin were abolished, and antigen-specific delayed-type hypersensitivity skin inflammatory responses were markedly impaired in arrhythmic hamsters. The SCN drives robust CRs in leukocyte trafficking and lymphoid clock gene expression; the latter of which is not expressed in the absence of melatonin. Robust entrainment of the circadian pacemaker provides a signal critical to diurnal rhythms in immunosurveilliance and optimal memory T-cell dependent immune responses. (C) 2013 Elsevier Inc. All rights reserved.
引用
收藏
页码:94 / 104
页数:11
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