Projects per year
Abstract
Though it has been shown that immunological functions of CD4+ T cells are time of day-dependent, the underlying molecular mechanisms remain largely obscure. To address the question whether T cells themselves harbor a functional clock driving circadian rhythms of immune function, we analyzed clock gene expression by qPCR in unstimulated CD4+ T cells and immune responses of PMA/ionomycin stimulated CD4+ T cells by FACS analysis purified from blood of healthy subjects at different time points throughout the day. Molecular clock as well as immune function was further analyzed in unstimulated T cells which were cultured in serum-free medium with circadian clock reporter systems. We found robust rhythms of clock gene expression as well as, after stimulation, IL-2, IL-4, IFN-γ production and CD40L expression in freshly isolated CD4+ T cells. Further analysis of IFN-γ and CD40L in cultivated T cells revealed that these parameters remain rhythmic in vitro. Moreover, circadian luciferase reporter activity in CD4+ T cells and in thymic sections from PER2::LUCIFERASE reporter mice suggest that endogenous T cell clock rhythms are self-sustained under constant culture conditions. Microarray analysis of stimulated CD4+ T cell cultures revealed regulation of the NF-κB pathway as a candidate mechanism mediating circadian immune responses. Collectively, these data demonstrate for the first time that CD4+ T cell responses are regulated by an intrinsic cellular circadian oscillator capable of driving rhythmic CD4+ T cell immune responses.
Original language | English |
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Article number | e29801 |
Journal | PLoS ONE |
Volume | 6 |
Issue number | 12 |
ISSN | 1553-7390 |
DOIs | |
Publication status | Published - 28.12.2011 |
Research Areas and Centers
- Academic Focus: Center for Infection and Inflammation Research (ZIEL)
Fingerprint
Dive into the research topics of 'Circadian clocks in mouse and human CD4+ T cells'. Together they form a unique fingerprint.Projects
- 2 Finished
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nvestigations into the molecular physiology of peripheral circadian clocks
Oster, H. (Principal Investigator (PI))
01.01.07 → 31.12.12
Project: DFG Projects › DFG Individual Projects
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Emmy Noether Research Group: Studies on the molecular physiology of peripheral circadian clocks
Oster, H. (Speaker, Coordinator)
01.01.07 → 31.12.12
Project: DFG Projects › DFG Scholarships: Emmy Noether Programme