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Circadian Clocks in Mouse and Human CD4+ T Cells

Leutz, Anton
Leliavski, Alexei
Skrum, Ludmila
Kovac, Judit
Benedict, Christian
Lange, Tanja
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Published in PLOS ONE. 2011, vol. 6, no. 12, e29801
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.
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BOLLINGER, Thomas et al. Circadian Clocks in Mouse and Human CD4+ T Cells. In: PLOS ONE, 2011, vol. 6, n° 12, p. e29801. doi: 10.1371/journal.pone.0029801 https://archive-ouverte.unige.ch/unige:37106

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Deposited on : 2014-06-03

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